rs3130618

Variant names:

• chr6-31664357-C-A
• rs3130618
• NM_033177.4:c.122G>T

Your query was ambiguous. Multiple possible variants found:

• chr6-31664357-C-A
• chr6-31664357-C-G
• chr6-31664357-C-T

Variant summary

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

The NM_033177.4(GPANK1):​c.122G>T​(p.Arg41Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 1,613,854 control chromosomes in the GnomAD database, including 26,676 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 0.17 (2376 hom., cov: 32)
  • Exomes 𝑓: 0.18 (24300 hom.)
• Consequence: GPANK1 NM_033177.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.47
• Publications: 91 publications found

Genes affected

GPANK1 (HGNC:13920): (G-patch domain and ankyrin repeats 1) This gene is located in a cluster of HLA-B-associated transcripts, which is included in the human major histocompatability complex III region. This gene encodes a protein which is thought to play a role in immunity. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Nov 2010]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0016124249).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPANK1	NM_033177.4	c.122G>T	p.Arg41Leu	missense_variant	Exon 2 of 3	ENST00000375896.9	NP_149417.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPANK1	ENST00000375896.9	c.122G>T	p.Arg41Leu	missense_variant	Exon 2 of 3	1	NM_033177.4	ENSP00000365060.4

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25650 AN: 152040 Hom.: 2376 Cov.: 32

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.0986

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.0786

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.150

GnomAD2 exomes AF: 0.145 AC: 36482 AN: 251328 AF XY: 0.145

Gnomad AFR exome AF: 0.198

Gnomad AMR exome AF: 0.0764

Gnomad ASJ exome AF: 0.113

Gnomad EAS exome AF: 0.0960

Gnomad FIN exome AF: 0.159

Gnomad NFE exome AF: 0.177

Gnomad OTH exome AF: 0.140

GnomAD4 exome AF: 0.176 AC: 257446 AN: 1461696 Hom.: 24300 Cov.: 33 AF XY: 0.174 AC XY: 126331 AN XY: 727164

African (AFR) AF: 0.206 AC: 6905 AN: 33478

American (AMR) AF: 0.0802 AC: 3588 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 3111 AN: 26136

East Asian (EAS) AF: 0.0466 AC: 1851 AN: 39700

South Asian (SAS) AF: 0.115 AC: 9908 AN: 86254

European-Finnish (FIN) AF: 0.160 AC: 8554 AN: 53410

Middle Eastern (MID) AF: 0.0915 AC: 528 AN: 5768

European-Non Finnish (NFE) AF: 0.192 AC: 213036 AN: 1111836

Other (OTH) AF: 0.165 AC: 9965 AN: 60392

GnomAD4 genome AF: 0.169 AC: 25650 AN: 152158 Hom.: 2376 Cov.: 32 AF XY: 0.164 AC XY: 12214 AN XY: 74382

African (AFR) AF: 0.193 AC: 8003 AN: 41490

American (AMR) AF: 0.0983 AC: 1504 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 398 AN: 3470

East Asian (EAS) AF: 0.0791 AC: 410 AN: 5182

South Asian (SAS) AF: 0.125 AC: 601 AN: 4824

European-Finnish (FIN) AF: 0.161 AC: 1709 AN: 10596

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.184 AC: 12501 AN: 67976

Other (OTH) AF: 0.149 AC: 315 AN: 2116

Alfa AF: 0.178 Hom.: 7773

Bravo AF: 0.166

TwinsUK AF: 0.190 AC: 706

ALSPAC AF: 0.193 AC: 745

ESP6500AA AF: 0.200 AC: 881

ESP6500EA AF: 0.179 AC: 1541

ExAC AF: 0.150 AC: 18218

Asia WGS AF: 0.0950 AC: 331 AN: 3478

EpiCase AF: 0.173

EpiControl AF: 0.165

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.23
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T;T;T;T;T;.;T;.
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.69	.;.;.;.;T;T;T;T
MetaRNN	Benign	0.0016	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.67	T
MutationAssessor	Benign	1.9	L;L;L;L;L;.;.;.
PhyloP100		3.5
PrimateAI	Benign	0.48	T
PROVEAN	Uncertain	-4.3	D;D;D;D;D;D;D;D
REVEL	Benign	0.14
Sift	Benign	0.057	T;T;T;T;T;T;T;T
Sift4G	Pathogenic	0.0	D;D;D;D;D;.;D;.
Polyphen		1.0	D;D;D;D;D;.;.;.
Vest4		0.25
MPC		0.95
ClinPred		0.030	T
GERP RS		5.2
Varity_R		0.72
gMVP		0.71
Mutation Taster		=96/4	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: rs3130618; hg19: chr6-31632134; COSMIC: COSV63263784; COSMIC: COSV63263784;