chr6-31662526-C-T

Variant names:

• chr6-31662526-C-T
• rs780938621
• NM_033177.4:c.811G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_033177.4(GPANK1):​c.811G>A​(p.Gly271Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,552 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: GPANK1 NM_033177.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.33
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36800724).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033177.4. 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
	GPANK1	NM_033177.4	MANE Select	c.811G>A	p.Gly271Arg	missense	Exon 3 of 3	NP_149417.1	O95872
	GPANK1	NM_001199237.1		c.811G>A	p.Gly271Arg	missense	Exon 4 of 4	NP_001186166.1	A0A024RCU2
	GPANK1	NM_001199238.1		c.811G>A	p.Gly271Arg	missense	Exon 4 of 4	NP_001186167.1	A0A024RCU2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPANK1	ENST00000375896.9	TSL:1 MANE Select	c.811G>A	p.Gly271Arg	missense	Exon 3 of 3	ENSP00000365060.4	O95872
	GPANK1	ENST00000375893.6	TSL:5	c.811G>A	p.Gly271Arg	missense	Exon 4 of 4	ENSP00000365057.2	O95872
	GPANK1	ENST00000375895.6	TSL:5	c.811G>A	p.Gly271Arg	missense	Exon 4 of 4	ENSP00000365059.2	O95872

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000407 AC: 1 AN: 245788 AF XY: 0.00000746

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000908

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460552 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 726596

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26116

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52288

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111886

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

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000851 AC: 1

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	0.28
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.072	T
Eigen	Pathogenic	0.79
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.047	D
MetaRNN	Benign	0.37	T
MetaSVM	Uncertain	0.077	D
MutationAssessor	Pathogenic	4.0	H
PhyloP100		3.3
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	0.32	N
REVEL	Uncertain	0.47
Sift	Benign	0.10	T
Sift4G	Benign	0.070	T
Polyphen		1.0	D
Vest4		0.22
MutPred		0.70		Gain of MoRF binding (P = 0.0312)
MVP		0.71
MPC		0.93
ClinPred		0.88	D
GERP RS		5.0
Varity_R		0.23
gMVP		0.77
Mutation Taster		=71/29	polymorphism

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: rs780938621; hg19: chr6-31630303;