2-30932150-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_024572.4(GALNT14):c.976G>A(p.Val326Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00367 in 1,566,258 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0021 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0038 (30 hom.)
• Consequence: GALNT14 NM_024572.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.582

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 Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.013418257).
• BP6: Variant 2-30932150-C-T is Benign according to our data. Variant chr2-30932150-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3045099.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GALNT14	NM_024572.4	c.976G>A	p.Val326Ile	missense_variant	10/15	ENST00000349752.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GALNT14	ENST00000349752.10	c.976G>A	p.Val326Ile	missense_variant	10/15	1	NM_024572.4	P1

Frequencies

GnomAD3 genomes AF: 0.00207 AC: 314 AN: 151888 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000702

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000917

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000754

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00380

Gnomad OTH AF: 0.00240

GnomAD3 exomes AF: 0.00150 AC: 321 AN: 214140 Hom.: 0 AF XY: 0.00138 AC XY: 160 AN XY: 116186

Gnomad AFR exome AF: 0.000642

Gnomad AMR exome AF: 0.00127

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000403

Gnomad FIN exome AF: 0.000766

Gnomad NFE exome AF: 0.00254

Gnomad OTH exome AF: 0.00163

GnomAD4 exome AF: 0.00385 AC: 5439 AN: 1414252 Hom.: 30 Cov.: 30 AF XY: 0.00360 AC XY: 2530 AN XY: 702482

Gnomad4 AFR exome AF: 0.000451

Gnomad4 AMR exome AF: 0.00123

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000278

Gnomad4 SAS exome AF: 0.000151

Gnomad4 FIN exome AF: 0.000703

Gnomad4 NFE exome AF: 0.00470

Gnomad4 OTH exome AF: 0.00358

GnomAD4 genome AF: 0.00207 AC: 314 AN: 152006 Hom.: 0 Cov.: 32 AF XY: 0.00182 AC XY: 135 AN XY: 74314

Gnomad4 AFR AF: 0.000700

Gnomad4 AMR AF: 0.000916

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000754

Gnomad4 NFE AF: 0.00380

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00300 Hom.: 3

Bravo AF: 0.00206

TwinsUK AF: 0.00378 AC: 14

ALSPAC AF: 0.00389 AC: 15

ESP6500AA AF: 0.00113 AC: 5

ESP6500EA AF: 0.00337 AC: 29

ExAC AF: 0.00151 AC: 183

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

GALNT14-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 10, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.56
Cadd	Benign	6.3
Dann	Benign	0.73
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.73	T;T;T;T
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.013	T;T;T;T
MetaSVM	Benign	-0.96	T
MutationTaster	Benign	0.91	N;N;N;N;N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	0.35	N;N;N;N
REVEL	Benign	0.047
Sift	Benign	1.0	T;T;T;T
Sift4G	Benign	1.0	T;T;T;.
Polyphen		0.0030	B;B;.;.
Vest4		0.16
MVP		0.21
MPC		0.19
ClinPred		0.0015	T
GERP RS		-4.1
Varity_R		0.018
gMVP		0.36

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: rs139793019; hg19: chr2-31155016; COSMIC: COSV61104789; COSMIC: COSV61104789;