chr7-152094468-G-A

Position:

• chr7-152094468-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_022087.4(GALNT11):​c.241G>A​(p.Asp81Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GALNT11 NM_022087.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.02

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 (HGNC:):

ACMG classification

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=0.1382002).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GALNT11	NM_022087.4	c.241G>A	p.Asp81Asn	missense_variant	2/12	ENST00000430044.7	NP_071370.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GALNT11	ENST00000430044.7	c.241G>A	p.Asp81Asn	missense_variant	2/12	5	NM_022087.4	ENSP00000395122.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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 26, 2024

The c.241G>A (p.D81N) alteration is located in exon 2 (coding exon 1) of the GALNT11 gene. This alteration results from a G to A substitution at nucleotide position 241, causing the aspartic acid (D) at amino acid position 81 to be replaced by an asparagine (N). 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	0.069
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	12
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0042	T;T;.;T;T;.;.;T;T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.72	.;T;T;T;T;.;T;T;T
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.14	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.72	T
MutationAssessor	Benign	0.92	L;.;.;.;L;L;L;.;.
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.23	N;N;N;N;N;N;N;N;N
REVEL	Benign	0.19
Sift	Benign	0.47	T;T;T;T;T;T;T;T;T
Sift4G	Benign	0.47	T;T;T;T;T;T;T;T;T
Polyphen		0.0	B;.;.;.;B;B;B;.;.
Vest4		0.22
MutPred		0.23		Loss of catalytic residue at D81 (P = 0.1616);Loss of catalytic residue at D81 (P = 0.1616);Loss of catalytic residue at D81 (P = 0.1616);Loss of catalytic residue at D81 (P = 0.1616);Loss of catalytic residue at D81 (P = 0.1616);Loss of catalytic residue at D81 (P = 0.1616);Loss of catalytic residue at D81 (P = 0.1616);Loss of catalytic residue at D81 (P = 0.1616);Loss of catalytic residue at D81 (P = 0.1616);
MVP		0.70
MPC		0.25
ClinPred		0.21	T
GERP RS		4.8
Varity_R		0.047
gMVP		0.41

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

Other links and lift over

dbSNP: rs2086248707; hg19: chr7-151791553;