2-30929432-C-A

Variant names:

• chr2-30929432-C-A
• rs531692673
• NM_024572.4:c.1114G>T

Variant summary

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

The NM_024572.4(GALNT14):​c.1114G>T​(p.Ala372Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000547 in 1,461,792 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: GALNT14 NM_024572.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.08

Genes affected

GALNT14 (HGNC:22946): (polypeptide N-acetylgalactosaminyltransferase 14) This gene encodes a Golgi protein which is a member of the polypeptide N-acetylgalactosaminyltransferase (ppGalNAc-Ts) protein family. These enzymes catalyze the transfer of N-acetyl-D-galactosamine (GalNAc) to the hydroxyl groups on serines and threonines in target peptides. The encoded protein has been shown to transfer GalNAc to large proteins like mucins. Alterations in this gene may play a role in cancer progression and response to chemotherapy. [provided by RefSeq, Jun 2016]

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=0.24320504).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GALNT14	NM_024572.4	c.1114G>T	p.Ala372Ser	missense_variant	Exon 11 of 15	ENST00000349752.10	NP_078848.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GALNT14	ENST00000349752.10	c.1114G>T	p.Ala372Ser	missense_variant	Exon 11 of 15	1	NM_024572.4	ENSP00000288988.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000547 AC: 8 AN: 1461792 Hom.: 0 Cov.: 30 AF XY: 0.00000688 AC XY: 5 AN XY: 727208

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000202

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 Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 16, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1114G>T (p.A372S) alteration is located in exon 11 (coding exon 11) of the GALNT14 gene. This alteration results from a G to T substitution at nucleotide position 1114, causing the alanine (A) at amino acid position 372 to be replaced by a serine (S). 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	0.095
BayesDel_addAF	Benign	-0.0045	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0093	.;T;.;.
Eigen	Benign	-0.00048
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.86	D;D;D;D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.24	T;T;T;T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	0.98	.;L;.;.
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.53	N;N;N;N
REVEL	Benign	0.072
Sift	Benign	0.23	T;T;T;T
Sift4G	Benign	0.32	T;T;T;.
Polyphen		0.075	B;B;.;.
Vest4		0.34
MutPred		0.34		.;Gain of helix (P = 0.0696);.;.;
MVP		0.66
MPC		0.40
ClinPred		0.74	D
GERP RS		5.2
Varity_R		0.11
gMVP		0.27

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: rs531692673; hg19: chr2-31152298;