12-89523004-G-T

Position:

chr12-89523004-G-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_003774.5(GALNT4):c.1546C>A(p.Gln516Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00735 in 1,613,866 control chromosomes in the GnomAD database, including 60 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0044 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0077 ( 60 hom. )

Consequence

GALNT4
NM_003774.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 6.51

Variant links:

Genes affected

GALNT4 (HGNC:4126): (polypeptide N-acetylgalactosaminyltransferase 4) This gene encodes a member of the UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase (GalNAc-T) family of enzymes. GalNAc-Ts initiate mucin-type O-linked glycosylation in the Golgi apparatus by catalyzing the transfer of GalNAc to serine and threonine residues on target proteins. They are characterized by an N-terminal transmembrane domain, a stem region, a lumenal catalytic domain containing a GT1 motif and Gal/GalNAc transferase motif, and a C-terminal ricin/lectin-like domain. GalNAc-Ts have different, but overlapping, substrate specificities and patterns of expression. In vitro, the encoded protein can complement other GalNAc-Ts in the complete O-glycosylation of the mucin-1 tandem repeat and can O-glycosylate the P-selectin glycoprotein ligand-1 molecule. The coding region of this gene is contained within a single exon. Fusion transcripts, which combine part of this gene with the 5' exons of the neighboring POC1B (POC1 centriolar protein homolog B) gene, also exist. [provided by RefSeq, Dec 2010]

GALNT4 links:

POC1B-GALNT4 (HGNC:42957): (POC1B-GALNT4 readthrough) This locus represents naturally occurring transcripts that splice the 5' exons of the POC1B (POC1 centriolar protein homolog B) gene on chromosome 12 to the GALNT4 (UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 4) gene, which is located within a POC1B intron. Alternative splicing results in two transcript variants, one of which encodes a fusion isoform that shares sequence identity with the products of each individual gene. [provided by RefSeq, Dec 2010]

POC1B-GALNT4 links:

POC1B (HGNC:30836): (POC1 centriolar protein B) POC1 proteins contain an N-terminal WD40 domain and a C-terminal coiled coil domain and are part of centrosomes. They play an important role in basal body and cilia formation. This gene encodes one of the two POC1 proteins found in humans. Mutation in this gene result in autosomal-recessive cone-rod dystrophy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2014]

POC1B links:

POC1B (HGNC:):

POC1B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0054709613).

BP6

Variant 12-89523004-G-T is Benign according to our data. Variant chr12-89523004-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 773664.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 60 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GALNT4	NM_003774.5 linkuse as main transcript	c.1546C>A	p.Gln516Lys	missense_variant	1/1	ENST00000529983.3	NP_003765.2	Q8N4A0-1
POC1B	NM_172240.3 linkuse as main transcript	c.100+2116C>A		intron_variant		ENST00000313546.8	NP_758440.1	Q8TC44-1A0MNP0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
GALNT4	ENST00000529983.3 linkuse as main transcript	c.1546C>A	p.Gln516Lys	missense_variant	1/1	6	NM_003774.5	ENSP00000436604.2	Q8N4A0-1
POC1B-GALNT4	ENST00000548729.5 linkuse as main transcript	c.1537C>A	p.Gln513Lys	missense_variant	3/3	2		ENSP00000447852.1	F8VUJ3
POC1B	ENST00000313546.8 linkuse as main transcript	c.100+2116C>A		intron_variant		1	NM_172240.3	ENSP00000323302.3	Q8TC44-1

Frequencies

GnomAD3 genomes

AF:

0.00442

AC:

672

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00138

Gnomad AMI

AF:

0.00440

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00546

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00792

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00437

AC:

1087

AN:

249012

Hom.:

AF XY:

0.00428

AC XY:

578

AN XY:

135114

show subpopulations

Gnomad AFR exome

AF:

0.00110

Gnomad AMR exome

AF:

0.000261

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000556

Gnomad FIN exome

AF:

0.00488

Gnomad NFE exome

AF:

0.00815

Gnomad OTH exome

AF:

0.00315

GnomAD4 exome

AF:

0.00766

AC:

11190

AN:

1461566

Hom.:

Cov.:

AF XY:

0.00745

AC XY:

5414

AN XY:

727046

show subpopulations

Gnomad4 AFR exome

AF:

0.00105

Gnomad4 AMR exome

AF:

0.000336

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000568

Gnomad4 FIN exome

AF:

0.00579

Gnomad4 NFE exome

AF:

0.00947

Gnomad4 OTH exome

AF:

0.00421

GnomAD4 genome

AF:

0.00441

AC:

672

AN:

152300

Hom.:

Cov.:

AF XY:

0.00432

AC XY:

322

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.00137

Gnomad4 AMR

AF:

0.000458

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00546

Gnomad4 NFE

AF:

0.00792

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00698

Hom.:

Bravo

AF:

0.00393

TwinsUK

AF:

0.0119

AC:

ALSPAC

AF:

0.00986

AC:

ESP6500AA

AF:

0.00137

AC:

ESP6500EA

AF:

0.00795

AC:

ExAC

AF:

0.00422

AC:

510

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00682

EpiControl

AF:

0.00694

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Oct 01, 2023	GALNT4: BP4, BS2; POC1B-GALNT4: BP4, BS2 -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 23, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.019

T;.

Eigen

Benign

-0.065

Eigen_PC

Benign

0.19

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.61

T;T

M_CAP

Benign

0.0050

MetaRNN

Benign

0.0055

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.080

N;.

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.28

N;N

REVEL

Benign

0.056

Sift

Benign

0.58

T;T

Sift4G

Benign

0.37

T;T

Polyphen

0.0010

B;B

Vest4

0.098

MVP

0.52

MPC

0.17

ClinPred

0.010

GERP RS

5.0

Varity_R

0.38

gMVP

0.44

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over