2-30912318-G-T

Variant names:

• chr2-30912318-G-T
• rs2288101
• NM_024572.4:c.1405C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024572.4(GALNT14):​c.1405C>A​(p.Gln469Lys) variant causes a missense change. The variant allele was found at a frequency of 0.233 in 1,613,674 control chromosomes in the GnomAD database, including 44,944 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.21 (3637 hom., cov: 32)
  • Exomes 𝑓: 0.24 (41307 hom.)
• Consequence: GALNT14 NM_024572.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.43
• Publications: 26 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0016799569).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.238 is higher than 0.05.

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.1405C>A	p.Gln469Lys	missense	Exon 14 of 15	NP_078848.2	Q96FL9-1
	GALNT14	NM_001253826.2		c.1420C>A	p.Gln474Lys	missense	Exon 15 of 16	NP_001240755.1	Q96FL9-3
	GALNT14	NM_001253827.2		c.1345C>A	p.Gln449Lys	missense	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.1405C>A	p.Gln469Lys	missense	Exon 14 of 15	ENSP00000288988.6	Q96FL9-1
	GALNT14	ENST00000324589.9	TSL:2	c.1420C>A	p.Gln474Lys	missense	Exon 15 of 16	ENSP00000314500.5	Q96FL9-3
	GALNT14	ENST00000406653.5	TSL:2	c.1345C>A	p.Gln449Lys	missense	Exon 16 of 17	ENSP00000385435.1	Q96FL9-4

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32543 AN: 151980 Hom.: 3636 Cov.: 32

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.242

Gnomad EAS AF: 0.222

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.207

GnomAD2 exomes AF: 0.226 AC: 56846 AN: 251290 AF XY: 0.231

Gnomad AFR exome AF: 0.158

Gnomad AMR exome AF: 0.170

Gnomad ASJ exome AF: 0.224

Gnomad EAS exome AF: 0.222

Gnomad FIN exome AF: 0.279

Gnomad NFE exome AF: 0.243

Gnomad OTH exome AF: 0.221

GnomAD4 exome AF: 0.235 AC: 343839 AN: 1461576 Hom.: 41307 Cov.: 33 AF XY: 0.236 AC XY: 171949 AN XY: 727094

African (AFR) AF: 0.157 AC: 5257 AN: 33478

American (AMR) AF: 0.174 AC: 7758 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.226 AC: 5915 AN: 26134

East Asian (EAS) AF: 0.223 AC: 8867 AN: 39696

South Asian (SAS) AF: 0.236 AC: 20375 AN: 86252

European-Finnish (FIN) AF: 0.277 AC: 14780 AN: 53372

Middle Eastern (MID) AF: 0.224 AC: 1292 AN: 5766

European-Non Finnish (NFE) AF: 0.239 AC: 265982 AN: 1111782

Other (OTH) AF: 0.225 AC: 13613 AN: 60382

GnomAD4 genome AF: 0.214 AC: 32567 AN: 152098 Hom.: 3637 Cov.: 32 AF XY: 0.214 AC XY: 15875 AN XY: 74332

African (AFR) AF: 0.157 AC: 6508 AN: 41506

American (AMR) AF: 0.180 AC: 2760 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.242 AC: 839 AN: 3470

East Asian (EAS) AF: 0.222 AC: 1144 AN: 5150

South Asian (SAS) AF: 0.236 AC: 1139 AN: 4818

European-Finnish (FIN) AF: 0.288 AC: 3046 AN: 10580

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.242 AC: 16418 AN: 67968

Other (OTH) AF: 0.212 AC: 446 AN: 2108

Alfa AF: 0.233 Hom.: 19354

Bravo AF: 0.205

TwinsUK AF: 0.234 AC: 867

ALSPAC AF: 0.247 AC: 951

ESP6500AA AF: 0.164 AC: 722

ESP6500EA AF: 0.242 AC: 2081

ExAC AF: 0.226 AC: 27435

Asia WGS AF: 0.239 AC: 834 AN: 3478

EpiCase AF: 0.246

EpiControl AF: 0.238

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	23
DANN	Benign	0.95
DEOGEN2	Benign	0.015	T
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.60	T
MetaRNN	Benign	0.0017	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		6.4
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.092
Sift	Benign	0.40	T
Sift4G	Benign	0.66	T
Polyphen		0.96	D
Vest4		0.18
MPC		0.87
ClinPred		0.034	T
GERP RS		5.0
Varity_R		0.66
gMVP		0.67
Mutation Taster		=87/13	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2288101; hg19: chr2-31135184; COSMIC: COSV61106014;