X-71592146-C-T

Variant names:

• chrX-71592146-C-T
• rs35103538
• NM_052957.5:c.84C>T

Variant summary

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

The NM_052957.5(GCNA):​c.84C>T​(p.Ser28Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000915 in 1,093,139 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 20)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: GCNA NM_052957.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0640
• 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: Uncertain_significance. The variant received 2 ACMG points.

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

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.84C>T	p.Ser28Ser	synonymous	Exon 3 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.84C>T	p.Ser28Ser	synonymous	Exon 3 of 13	ENSP00000362800.3	Q96QF7
	GCNA	ENST00000373695.1	TSL:1	c.84C>T	p.Ser28Ser	synonymous	Exon 2 of 12	ENSP00000362799.1	Q96QF7
	GCNA	ENST00000917930.1		c.84C>T	p.Ser28Ser	synonymous	Exon 3 of 13	ENSP00000587989.1

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD4 exome AF: 9.15e-7 AC: 1 AN: 1093139 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 359011

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

African (AFR) AF: 0.00 AC: 0 AN: 26305

American (AMR) AF: 0.00 AC: 0 AN: 35122

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19337

East Asian (EAS) AF: 0.00 AC: 0 AN: 30172

South Asian (SAS) AF: 0.00 AC: 0 AN: 53880

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40512

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4125

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 837754

Other (OTH) AF: 0.00 AC: 0 AN: 45932

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 20

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.8
DANN	Benign	0.41
PhyloP100		0.064

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.41		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.41		Position offset: 22

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

Other links and lift over

dbSNP: rs35103538; hg19: chrX-70811996;