Genetic Variant GCNA:p.Ala68Pro (chrX-71594760-G-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_052957.5(GCNA):c.202G>C(p.Ala68Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., 0 hem., cov: 17)

Exomes 𝑓: 0.0000019 ( 0 hom. 0 hem. )

Failed GnomAD Quality Control

Consequence

GCNA
NM_052957.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.30

Variant links:

Genes affected

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

GCNA links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.04656163).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GCNA	NM_052957.5 link	c.202G>C	p.Ala68Pro	missense_variant	Exon 6 of 13	ENST00000373696.8	NP_443189.1	Q96QF7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GCNA	ENST00000373696.8 link	c.202G>C	p.Ala68Pro	missense_variant	Exon 6 of 13	1	NM_052957.5	ENSP00000362800.3		Q96QF7
GCNA	ENST00000373695.1 link	c.202G>C	p.Ala68Pro	missense_variant	Exon 5 of 12	1		ENSP00000362799.1		Q96QF7

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

98324

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

22638

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000210

AC:

AN:

142784

Hom.:

AF XY:

0.00

AC XY:

AN XY:

45334

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000147

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000192

AC:

AN:

1040351

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

329529

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000801

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

98324

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

22638

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000166

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 12, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.202G>C (p.A68P) alteration is located in exon 6 (coding exon 5) of the ACRC gene. This alteration results from a G to C substitution at nucleotide position 202, causing the alanine (A) at amino acid position 68 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

Benign

0.097

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.037

DANN

Benign

0.31

DEOGEN2

Benign

0.0096

T;T

FATHMM_MKL

Benign

0.0048

LIST_S2

Benign

0.35

.;T

M_CAP

Benign

0.0029

MetaRNN

Benign

0.047

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.46

N;N

PrimateAI

Benign

0.44

PROVEAN

Benign

0.17

N;N

REVEL

Benign

0.022

Sift

Benign

0.30

T;T

Sift4G

Benign

0.36

T;T

Polyphen

0.0

B;B

Vest4

0.044

MutPred

0.28

Gain of glycosylation at A68 (P = 0.0046);Gain of glycosylation at A68 (P = 0.0046);

MVP

0.23

MPC

0.27

ClinPred

0.041

GERP RS

-5.3

Varity_R

0.057

gMVP

0.061

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over