X-156025065-C-G

Variant names:

• chrX-156025065-C-G
• rs772298164
• ENST00000359512.8:c.1268C>G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The ENST00000359512.8(WASH6P):​c.1268C>G​(p.Ser423Trp) variant causes a missense change. The variant allele was found at a frequency of 0.000079 in 151,906 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S423L) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000079 (0 hom., 4 hem., cov: 40)
  • Exomes 𝑓: 0.0000071 (0 hom. 1 hem.)
  • Failed GnomAD Quality Control
• Consequence: WASH6P ENST00000359512.8 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.26

Genes affected

WASH6P (HGNC:31685): (WASP family homolog 6, pseudogene) Predicted to enable alpha-tubulin binding activity. Predicted to be involved in Arp2/3 complex-mediated actin nucleation and retrograde transport, endosome to Golgi. Predicted to be located in early endosome and recycling endosome. Predicted to be part of WASH complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BS2: High Hemizygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WASH6P		n.156025065C>G		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WASH6P	ENST00000359512.8	c.1268C>G	p.Ser423Trp	missense_variant	Exon 9 of 10	6		ENSP00000504557.1

Frequencies

GnomAD3 genomes AF: 0.0000791 AC: 12 AN: 151790 Hom.: 0 Cov.: 40 AF XY: 0.0000540 AC XY: 4 AN XY: 74112

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000655

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: 0.000960

GnomAD3 exomes AF: 0.0000195 AC: 3 AN: 153798 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 81984

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000121

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: 0.00000715 AC: 10 AN: 1399518 Hom.: 0 Cov.: 32 AF XY: 0.00000145 AC XY: 1 AN XY: 691450

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000106

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: 9.29e-7

Gnomad4 OTH exome AF: 0.0000860

GnomAD4 genome AF: 0.0000790 AC: 12 AN: 151906 Hom.: 0 Cov.: 40 AF XY: 0.0000539 AC XY: 4 AN XY: 74236

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000655

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: 0.000950

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Uncertain	24
DANN	Uncertain	0.99

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs772298164; hg19: chrX-155254730;