Variant 7-152100800-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001371468.1(GALNT11):c.1A>G(p.Met1?) variant causes a start lost, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,613,450 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

GALNT11
NM_001371468.1 start_lost, splice_region

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.62

Variant links:

Genes affected

GALNT11 (HGNC:19875): (polypeptide N-acetylgalactosaminyltransferase 11) Enables Notch binding activity and polypeptide N-acetylgalactosaminyltransferase activity. Involved in protein O-linked glycosylation via threonine. Predicted to be located in Golgi membrane. Predicted to be active in Golgi apparatus. [provided by Alliance of Genome Resources, Apr 2022]

GALNT11 links:

GALNT11 (HGNC:):

GALNT11 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GALNT11	NM_022087.4 linkuse as main transcript	c.298A>G	p.Met100Val	missense_variant, splice_region_variant	3/12	ENST00000430044.7	NP_071370.2	Q8NCW6-1A0A090N7X6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GALNT11	ENST00000430044.7 linkuse as main transcript	c.298A>G	p.Met100Val	missense_variant, splice_region_variant	3/12	5	NM_022087.4	ENSP00000395122.2		Q8NCW6-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461240

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726948

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152210

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000192

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

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

Feb 28, 2023

The c.298A>G (p.M100V) alteration is located in exon 3 (coding exon 2) of the GALNT11 gene. This alteration results from a A to G substitution at nucleotide position 298, causing the methionine (M) at amino acid position 100 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

0.30

BayesDel_addAF

Pathogenic

0.38

BayesDel_noAF

Pathogenic

0.31

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.0061

T;T;.;.;T;T

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.0014

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.56

.;T;.;T;T;D

M_CAP

Uncertain

0.087

MetaRNN

Uncertain

0.48

T;T;T;T;T;T

MetaSVM

Benign

-0.75

MutationAssessor

Uncertain

2.5

M;M;M;M;.;.

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-0.99

N;N;N;.;N;N

REVEL

Uncertain

0.58

Sift

Benign

0.38

T;T;D;.;D;D

Sift4G

Benign

0.92

T;T;T;T;T;T

Polyphen

0.0040

B;B;B;B;.;.

Vest4

0.82

MutPred

0.39

Loss of disorder (P = 0.0995);Loss of disorder (P = 0.0995);Loss of disorder (P = 0.0995);Loss of disorder (P = 0.0995);Loss of disorder (P = 0.0995);Loss of disorder (P = 0.0995);

MVP

0.71

MPC

0.30

ClinPred

0.81

GERP RS

4.9

Varity_R

0.17

gMVP

0.63

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