Variant 9-135624201-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_182974.3(GLT6D1):c.727A>G(p.Ile243Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000336 in 1,612,222 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00025 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00034 ( 0 hom. )

Consequence

GLT6D1
NM_182974.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.651

Variant links:

Genes affected

GLT6D1 (HGNC:23671): (glycosyltransferase 6 domain containing 1) The GT6 glycosyltransferases gene family, which includes the ABO blood group (ABO; MIM 110300) and GLT6D1, shows a complex evolution pattern, with multiple events of gain and loss in different mammal species. In humans, the ABO gene is considered the sole functional member, although the O allele is null and is fixed in certain populations (summary by Casals et al. (2009) [PubMed 19218399]).[supplied by OMIM, Jan 2011]

GLT6D1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04412213).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLT6D1	NM_182974.3 linkuse as main transcript	c.727A>G	p.Ile243Val	missense_variant	5/5	ENST00000371763.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLT6D1	ENST00000371763.6 linkuse as main transcript	c.727A>G	p.Ile243Val	missense_variant	5/5	1	NM_182974.3	P1

Frequencies

GnomAD3 genomes

AF:

0.000250

AC:

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000529

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000235

AC:

AN:

247058

Hom.:

AF XY:

0.000239

AC XY:

AN XY:

133948

show subpopulations

Gnomad AFR exome

AF:

0.0000647

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:

0.0000465

Gnomad NFE exome

AF:

0.000489

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000345

AC:

503

AN:

1459988

Hom.:

Cov.:

AF XY:

0.000340

AC XY:

247

AN XY:

726194

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.0000451

Gnomad4 ASJ exome

AF:

0.0000384

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.000434

Gnomad4 OTH exome

AF:

0.000182

GnomAD4 genome

AF:

0.000250

AC:

AN:

152234

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000529

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000448

Hom.:

Bravo

AF:

0.000242

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000487

AC:

ExAC

AF:

0.000323

AC:

EpiCase

AF:

0.000491

EpiControl

AF:

0.000119

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 23, 2021

The c.727A>G (p.I243V) alteration is located in exon 5 (coding exon 4) of the GLT6D1 gene. This alteration results from a A to G substitution at nucleotide position 727, causing the isoleucine (I) at amino acid position 243 to be replaced by a valine (V). 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

0.10

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.73

Cadd

Benign

0.078

Dann

Benign

0.42

DEOGEN2

Benign

0.0050

T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.029

LIST_S2

Benign

0.29

T;T

M_CAP

Benign

0.00089

MetaRNN

Benign

0.044

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.3

L;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.31

PROVEAN

Benign

0.070

N;.

REVEL

Benign

0.018

Sift

Benign

0.39

T;.

Sift4G

Benign

0.52

T;T

Polyphen

0.016

B;.

Vest4

0.026

MVP

0.048

MPC

0.014

ClinPred

0.045

GERP RS

-4.0

Varity_R

0.037

gMVP

0.10

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