6-31662363-C-G

Variant names:

• chr6-31662363-C-G
• rs565313993
• NM_033177.4:c.974G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_033177.4(GPANK1):​c.974G>C​(p.Arg325Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,912 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R325W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: GPANK1 NM_033177.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.37
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24333811).

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.974G>C	p.Arg325Pro	missense	Exon 3 of 3	NP_149417.1	O95872
	GPANK1	NM_001199237.1		c.974G>C	p.Arg325Pro	missense	Exon 4 of 4	NP_001186166.1	A0A024RCU2
	GPANK1	NM_001199238.1		c.974G>C	p.Arg325Pro	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.974G>C	p.Arg325Pro	missense	Exon 3 of 3	ENSP00000365060.4	O95872
	GPANK1	ENST00000375893.6	TSL:5	c.974G>C	p.Arg325Pro	missense	Exon 4 of 4	ENSP00000365057.2	O95872
	GPANK1	ENST00000375895.6	TSL:5	c.974G>C	p.Arg325Pro	missense	Exon 4 of 4	ENSP00000365059.2	O95872

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000407 AC: 1 AN: 245788 AF XY: 0.00

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: 0.0000463

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459912 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 726232

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

American (AMR) AF: 0.00 AC: 0 AN: 44614

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26072

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86100

European-Finnish (FIN) AF: 0.0000191 AC: 1 AN: 52302

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111556

Other (OTH) AF: 0.00 AC: 0 AN: 60334

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.065	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0035	T
Eigen	Benign	0.092
Eigen_PC	Benign	0.011
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		1.4
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.11
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.99	D
Vest4		0.35
MutPred		0.32		Loss of MoRF binding (P = 5e-04)
MVP		0.37
MPC		0.86
ClinPred		0.80	D
GERP RS		3.1
Varity_R		0.18
gMVP		0.75
Mutation Taster		=79/21	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: rs565313993; hg19: chr6-31630140;