12-89523034-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_003774.5(GALNT4):c.1516G>A(p.Val506Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.317 in 1,613,338 control chromosomes in the GnomAD database, including 84,836 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.28 ( 6488 hom., cov: 32)

Exomes 𝑓: 0.32 ( 78348 hom. )

Consequence

GALNT4
NM_003774.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.51

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016531348).

BP6

Variant 12-89523034-C-T is Benign according to our data. Variant chr12-89523034-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GALNT4	NM_003774.5 link	c.1516G>A	p.Val506Ile	missense_variant	Exon 1 of 1	ENST00000529983.3	NP_003765.2	Q8N4A0-1
POC1B	NM_172240.3 link	c.100+2086G>A		intron_variant	Intron 2 of 11	ENST00000313546.8	NP_758440.1	Q8TC44-1A0MNP0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GALNT4	ENST00000529983.3 link	c.1516G>A	p.Val506Ile	missense_variant	Exon 1 of 1	6	NM_003774.5	ENSP00000436604.2	Q8N4A0-1
POC1B-GALNT4	ENST00000548729.5 link	c.1507G>A	p.Val503Ile	missense_variant	Exon 3 of 3	2		ENSP00000447852.1	F8VUJ3
POC1B	ENST00000313546.8 link	c.100+2086G>A		intron_variant	Intron 2 of 11	1	NM_172240.3	ENSP00000323302.3	Q8TC44-1

Frequencies

GnomAD3 genomes

AF:

0.280

AC:

42573

AN:

151968

Hom.:

6487

Cov.:

show subpopulations

Gnomad AFR

AF:

0.180

Gnomad AMI

AF:

0.509

Gnomad AMR

AF:

0.272

Gnomad ASJ

AF:

0.303

Gnomad EAS

AF:

0.137

Gnomad SAS

AF:

0.182

Gnomad FIN

AF:

0.333

Gnomad MID

AF:

0.255

Gnomad NFE

AF:

0.348

Gnomad OTH

AF:

0.287

GnomAD3 exomes

AF:

0.278

AC:

68996

AN:

248526

Hom.:

10482

AF XY:

0.276

AC XY:

37270

AN XY:

134846

show subpopulations

Gnomad AFR exome

AF:

0.174

Gnomad AMR exome

AF:

0.216

Gnomad ASJ exome

AF:

0.304

Gnomad EAS exome

AF:

0.137

Gnomad SAS exome

AF:

0.178

Gnomad FIN exome

AF:

0.342

Gnomad NFE exome

AF:

0.344

Gnomad OTH exome

AF:

0.298

GnomAD4 exome

AF:

0.321

AC:

469391

AN:

1461250

Hom.:

78348

Cov.:

AF XY:

0.317

AC XY:

230737

AN XY:

726866

show subpopulations

Gnomad4 AFR exome

AF:

0.186

Gnomad4 AMR exome

AF:

0.223

Gnomad4 ASJ exome

AF:

0.307

Gnomad4 EAS exome

AF:

0.157

Gnomad4 SAS exome

AF:

0.181

Gnomad4 FIN exome

AF:

0.339

Gnomad4 NFE exome

AF:

0.347

Gnomad4 OTH exome

AF:

0.305

GnomAD4 genome

AF:

0.280

AC:

42591

AN:

152088

Hom.:

6488

Cov.:

AF XY:

0.276

AC XY:

20536

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.180

Gnomad4 AMR

AF:

0.271

Gnomad4 ASJ

AF:

0.303

Gnomad4 EAS

AF:

0.137

Gnomad4 SAS

AF:

0.181

Gnomad4 FIN

AF:

0.333

Gnomad4 NFE

AF:

0.348

Gnomad4 OTH

AF:

0.289

Alfa

AF:

0.327

Hom.:

21127

Bravo

AF:

0.268

TwinsUK

AF:

0.352

AC:

1307

ALSPAC

AF:

0.358

AC:

1378

ESP6500AA

AF:

0.179

AC:

657

ESP6500EA

AF:

0.343

AC:

2808

ExAC

AF:

0.277

AC:

33402

Asia WGS

AF:

0.215

AC:

749

AN:

3478

EpiCase

AF:

0.343

EpiControl

AF:

0.340

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.42

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.039

T;.

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.83

T;T

MetaRNN

Benign

0.0017

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

M;.

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.70

N;N

REVEL

Benign

0.21

Sift

Uncertain

0.0070

D;D

Sift4G

Benign

0.076

T;T

Polyphen

0.88

P;P

Vest4

0.12

MPC

0.48

ClinPred

0.051

GERP RS

5.9

Varity_R

0.60

gMVP

0.37

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over