6-31663985-C-G

Position:

• chr6-31663985-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_033177.4(GPANK1):​c.494G>C​(p.Arg165Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GPANK1 NM_033177.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.52

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPANK1	NM_033177.4	c.494G>C	p.Arg165Pro	missense_variant	2/3	ENST00000375896.9	NP_149417.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPANK1	ENST00000375896.9	c.494G>C	p.Arg165Pro	missense_variant	2/3	1	NM_033177.4	ENSP00000365060.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 15, 2022

The c.494G>C (p.R165P) alteration is located in exon 2 (coding exon 1) of the GPANK1 gene. This alteration results from a G to C substitution at nucleotide position 494, causing the arginine (R) at amino acid position 165 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.78
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.11
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.047	T;T;T;T;T
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.81	.;.;.;.;T
M_CAP	Benign	0.043	D
MetaRNN	Uncertain	0.68	D;D;D;D;D
MetaSVM	Benign	-0.30	T
MutationAssessor	Pathogenic	3.3	M;M;M;M;M
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-2.7	D;D;D;D;D
REVEL	Uncertain	0.42
Sift	Uncertain	0.022	D;D;D;D;D
Sift4G	Uncertain	0.043	D;D;D;D;D
Polyphen		1.0	D;D;D;D;D
Vest4		0.63
MutPred		0.63		Loss of MoRF binding (P = 0.0018);Loss of MoRF binding (P = 0.0018);Loss of MoRF binding (P = 0.0018);Loss of MoRF binding (P = 0.0018);Loss of MoRF binding (P = 0.0018);
MVP		0.80
MPC		1.0
ClinPred		0.99	D
GERP RS		5.3
Varity_R		0.47
gMVP		0.83

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-31631762;