X-71597991-A-G

Variant names:

• chrX-71597991-A-G
• rs1602176785
• NM_052957.5:c.263A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_052957.5(GCNA):​c.263A>G​(p.His88Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H88N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 23)
• Consequence: GCNA NM_052957.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.687
• Publications: 0 publications found

Genes affected

GCNA (HGNC:15805): (germ cell nuclear acidic peptidase) Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04372686).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052957.5. 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
	GCNA	NM_052957.5	MANE Select	c.263A>G	p.His88Arg	missense	Exon 7 of 13	NP_443189.1	Q96QF7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GCNA	ENST00000373696.8	TSL:1 MANE Select	c.263A>G	p.His88Arg	missense	Exon 7 of 13	ENSP00000362800.3	Q96QF7
	GCNA	ENST00000373695.1	TSL:1	c.263A>G	p.His88Arg	missense	Exon 6 of 12	ENSP00000362799.1	Q96QF7
	GCNA	ENST00000917930.1		c.263A>G	p.His88Arg	missense	Exon 7 of 13	ENSP00000587989.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 23

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	0.065
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.67
DANN	Benign	0.40
DEOGEN2	Benign	0.021	T
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.32	T
M_CAP	Benign	0.0083	T
MetaRNN	Benign	0.044	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PhyloP100		-0.69
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.73	N
REVEL	Benign	0.072
Sift	Uncertain	0.016	D
Sift4G	Benign	0.31	T
Polyphen		0.11	B
Vest4		0.11
MutPred		0.15		Gain of methylation at K93 (P = 0.0567)
MVP		0.068
MPC		0.31
ClinPred		0.040	T
GERP RS		-1.5
Varity_R		0.077
gMVP		0.029
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: rs1602176785; hg19: chrX-70817841;