chr2-30924796-C-G

Variant names:

• chr2-30924796-C-G
• rs779498589
• NM_024572.4:c.1179G>C

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.1179G>C​(p.Lys393Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,613,928 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: GALNT14 NM_024572.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.696
• Publications: 1 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=0.12066859).

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.1179G>C	p.Lys393Asn	missense	Exon 12 of 15	NP_078848.2	Q96FL9-1
	GALNT14	NM_001253826.2		c.1194G>C	p.Lys398Asn	missense	Exon 13 of 16	NP_001240755.1	Q96FL9-3
	GALNT14	NM_001253827.2		c.1119G>C	p.Lys373Asn	missense	Exon 14 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.1179G>C	p.Lys393Asn	missense	Exon 12 of 15	ENSP00000288988.6	Q96FL9-1
	GALNT14	ENST00000324589.9	TSL:2	c.1194G>C	p.Lys398Asn	missense	Exon 13 of 16	ENSP00000314500.5	Q96FL9-3
	GALNT14	ENST00000406653.5	TSL:2	c.1119G>C	p.Lys373Asn	missense	Exon 14 of 17	ENSP00000385435.1	Q96FL9-4

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152188 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000239 AC: 6 AN: 251356 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000174

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461740 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727170

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.000157 AC: 7 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86228

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5686

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111986

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152188 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74350

African (AFR) AF: 0.00 AC: 0 AN: 41444

American (AMR) AF: 0.0000655 AC: 1 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000264

ExAC AF: 0.0000247 AC: 3

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.44
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.0071	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		0.70
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.062
Sift	Benign	0.082	T
Sift4G	Benign	0.10	T
Polyphen		0.22	B
Vest4		0.25
MutPred		0.38		Loss of MoRF binding (P = 0.0391)
MVP		0.47
MPC		0.27
ClinPred		0.35	T
GERP RS		0.83
Varity_R		0.19
gMVP		0.63
Mutation Taster		=67/33	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

dbSNP: rs779498589; hg19: chr2-31147662;