Variant 4-172348530-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001034845.3(GALNTL6):c.394C>T(p.His132Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00016 in 1,611,190 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

GALNTL6
NM_001034845.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.97

Variant links:

Genes affected

GALNTL6 (HGNC:33844): (polypeptide N-acetylgalactosaminyltransferase like 6) Enables polypeptide N-acetylgalactosaminyltransferase activity. Involved in protein O-linked glycosylation via threonine. Predicted to be located in Golgi membrane. Predicted to be integral component of membrane. Predicted to be active in Golgi apparatus. [provided by Alliance of Genome Resources, Apr 2022]

GALNTL6 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09393051).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
GALNTL6	NM_001034845.3 linkuse as main transcript	c.394C>T	p.His132Tyr	missense_variant	5/13	ENST00000506823.6
GALNTL6	XM_017008244.3 linkuse as main transcript	c.418C>T	p.His140Tyr	missense_variant	4/12
GALNTL6	XM_011531993.3 linkuse as main transcript	c.157C>T	p.His53Tyr	missense_variant	4/12
GALNTL6	XM_017008243.3 linkuse as main transcript	c.394C>T	p.His132Tyr	missense_variant	5/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GALNTL6	ENST00000506823.6 linkuse as main transcript	c.394C>T	p.His132Tyr	missense_variant	5/13	1	NM_001034845.3	P1	Q49A17-1
GALNTL6	ENST00000508122.5 linkuse as main transcript	c.343C>T	p.His115Tyr	missense_variant	4/12	1			Q49A17-2
GALNTL6	ENST00000457021.1 linkuse as main transcript	n.343C>T		non_coding_transcript_exon_variant	3/6	1

Frequencies

GnomAD3 genomes

AF:

0.000243

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000412

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000136

AC:

AN:

249384

Hom.:

AF XY:

0.000163

AC XY:

AN XY:

134776

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000295

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000292

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000151

AC:

220

AN:

1458890

Hom.:

Cov.:

AF XY:

0.000153

AC XY:

111

AN XY:

725726

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000449

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000189

Gnomad4 OTH exome

AF:

0.0000829

GnomAD4 genome

AF:

0.000243

AC:

AN:

152300

Hom.:

Cov.:

AF XY:

0.000228

AC XY:

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.000192

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000412

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000288

Hom.:

Bravo

AF:

0.000196

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.0000741

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000219

EpiControl

AF:

0.000178

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 08, 2022

The c.394C>T (p.H132Y) alteration is located in exon 5 (coding exon 4) of the GALNTL6 gene. This alteration results from a C to T substitution at nucleotide position 394, causing the histidine (H) at amino acid position 132 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.058

T;.

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.049

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.86

D;T

M_CAP

Benign

0.019

MetaRNN

Benign

0.094

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

N;.

MutationTaster

Benign

0.97

N;N

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-1.3

N;N

REVEL

Benign

0.033

Sift

Uncertain

0.021

D;D

Sift4G

Uncertain

0.030

D;T

Polyphen

0.28

B;.

Vest4

0.33

MVP

0.64

MPC

0.66

ClinPred

0.11

GERP RS

4.4

Varity_R

0.10

gMVP

0.56

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