chr7-152103203-G-A

Position:

• chr7-152103203-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_022087.4(GALNT11):​c.511G>A​(p.Val171Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GALNT11 NM_022087.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.07

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]

LOC731075 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.762

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GALNT11	NM_022087.4	c.511G>A	p.Val171Met	missense_variant	4/12	ENST00000430044.7	NP_071370.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GALNT11	ENST00000430044.7	c.511G>A	p.Val171Met	missense_variant	4/12	5	NM_022087.4	ENSP00000395122.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 06, 2022

The c.511G>A (p.V171M) alteration is located in exon 4 (coding exon 3) of the GALNT11 gene. This alteration results from a G to A substitution at nucleotide position 511, causing the valine (V) at amino acid position 171 to be replaced by a methionine (M). 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	0.19
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.070
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.080	T;T;.;.;T
Eigen	Pathogenic	0.77
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.90	.;D;.;D;D
M_CAP	Benign	0.065	D
MetaRNN	Pathogenic	0.76	D;D;D;D;D
MetaSVM	Uncertain	-0.11	T
MutationAssessor	Pathogenic	3.3	M;M;M;M;.
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-1.9	N;N;N;.;N
REVEL	Uncertain	0.38
Sift	Uncertain	0.0030	D;D;D;.;D
Sift4G	Benign	0.068	T;T;T;T;T
Polyphen		0.95	P;P;D;D;.
Vest4		0.67
MutPred		0.64		Loss of stability (P = 0.0881);Loss of stability (P = 0.0881);Loss of stability (P = 0.0881);Loss of stability (P = 0.0881);Loss of stability (P = 0.0881);
MVP		0.76
MPC		0.92
ClinPred		0.95	D
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.55
gMVP		0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

Other links and lift over

dbSNP: rs997293525; hg19: chr7-151800288;