2-30912341-A-T

Variant names:

• chr2-30912341-A-T
• NM_024572.4:c.1382T>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024572.4(GALNT14):​c.1382T>A​(p.Val461Glu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,544 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 18/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: GALNT14 NM_024572.4 missense, splice_region
• Scores: Splicing: ADA: 0.00002125
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 2.97
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.102421194).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024572.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GALNT14	NM_024572.4	MANE Select	c.1382T>A	p.Val461Glu	missense splice_region	Exon 14 of 15	NP_078848.2	Q96FL9-1
	GALNT14	NM_001253826.2		c.1397T>A	p.Val466Glu	missense splice_region	Exon 15 of 16	NP_001240755.1	Q96FL9-3
	GALNT14	NM_001253827.2		c.1322T>A	p.Val441Glu	missense splice_region	Exon 16 of 17	NP_001240756.1	Q96FL9-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GALNT14	ENST00000349752.10	TSL:1 MANE Select	c.1382T>A	p.Val461Glu	missense splice_region	Exon 14 of 15	ENSP00000288988.6	Q96FL9-1
	GALNT14	ENST00000324589.9	TSL:2	c.1397T>A	p.Val466Glu	missense splice_region	Exon 15 of 16	ENSP00000314500.5	Q96FL9-3
	GALNT14	ENST00000406653.5	TSL:2	c.1322T>A	p.Val441Glu	missense splice_region	Exon 16 of 17	ENSP00000385435.1	Q96FL9-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461544 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727060

African (AFR) AF: 0.00 AC: 0 AN: 33458

American (AMR) AF: 0.00 AC: 0 AN: 44676

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26108

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86200

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53392

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111890

Other (OTH) AF: 0.00 AC: 0 AN: 60372

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	GALNT14-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	16
DANN	Benign	0.54
DEOGEN2	Benign	0.0044	T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.40	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.20	N
PhyloP100		3.0
PrimateAI	Benign	0.30	T
PROVEAN	Benign	4.0	N
REVEL	Benign	0.064
Sift	Benign	1.0	T
Sift4G	Benign	0.70	T
Polyphen		0.0	B
Vest4		0.21
MutPred		0.74		Gain of disorder (P = 0.0092)
MVP		0.23
MPC		0.37
ClinPred		0.53	D
GERP RS		2.4
Varity_R		0.19
gMVP		0.49
Mutation Taster		=77/23	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000021
dbscSNV1_RF	Benign	0.036
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

Other links and lift over

hg19: chr2-31135207;