X-71592567-C-T

Variant names:

• chrX-71592567-C-T
• rs2040637035
• NM_052957.5:c.137C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_052957.5(GCNA):​c.137C>T​(p.Ala46Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 14)
  • Exomes 𝑓: 0.0000039 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: GCNA NM_052957.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.18
• 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.

• BP6: Variant X-71592567-C-T is Benign according to our data. Variant chrX-71592567-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3853268.Status of the report is criteria_provided_single_submitter, 1 stars.

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.137C>T	p.Ala46Val	missense	Exon 4 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.137C>T	p.Ala46Val	missense	Exon 4 of 13	ENSP00000362800.3	Q96QF7
	GCNA	ENST00000373695.1	TSL:1	c.137C>T	p.Ala46Val	missense	Exon 3 of 12	ENSP00000362799.1	Q96QF7
	GCNA	ENST00000917930.1		c.137C>T	p.Ala46Val	missense	Exon 4 of 13	ENSP00000587989.1

Frequencies

GnomAD3 genomes Cov.: 14

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000389 AC: 4 AN: 1027516 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 321848

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000459 AC: 1 AN: 21769

American (AMR) AF: 0.00 AC: 0 AN: 22601

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17492

East Asian (EAS) AF: 0.00 AC: 0 AN: 27931

South Asian (SAS) AF: 0.00 AC: 0 AN: 44387

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37945

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3642

European-Non Finnish (NFE) AF: 0.00000371 AC: 3 AN: 808704

Other (OTH) AF: 0.00 AC: 0 AN: 43045

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0188335), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 14

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.14
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.044
DANN	Benign	0.68
DEOGEN2	Benign	0.011	T
FATHMM_MKL	Benign	0.00041	N
LIST_S2	Benign	0.33	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.037	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		-1.2
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.23	N
REVEL	Benign	0.018
Sift	Uncertain	0.0080	D
Sift4G	Benign	0.90	T
Polyphen		0.0	B
Vest4		0.035
MutPred		0.18		Gain of methylation at K43 (P = 0.0816)
MVP		0.068
MPC		0.21
ClinPred		0.068	T
GERP RS		-4.2
Varity_R		0.040
gMVP		0.040
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.45		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.45		Position offset: -2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2040637035; hg19: chrX-70812417;