rs1555241837

chr12-105162776-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_015275.3(WASHC4):c.3088A>G(p.Ser1030Gly) variant causes a missense change. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: WASHC4 NM_015275.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.01

Genes affected

WASHC4 (HGNC:29174): (WASH complex subunit 4) This gene encodes a component of the WASH complex, which functions in the intracellular transport of endosomes. Mutations in this gene have been detected in individuals with autosomal recessive cognitive disability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WASHC4	NM_015275.3	c.3088A>G	p.Ser1030Gly	missense_variant	30/33	ENST00000332180.10
WASHC4	NM_001293640.2	c.3091A>G	p.Ser1031Gly	missense_variant	30/33
WASHC4	XM_011538073.4	c.2953A>G	p.Ser985Gly	missense_variant	29/32
WASHC4	XM_011538074.3	c.2524A>G	p.Ser842Gly	missense_variant	24/27

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WASHC4	ENST00000332180.10	c.3088A>G	p.Ser1030Gly	missense_variant	30/33	1	NM_015275.3	A1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1443802 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 719414

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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 Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Dec 17, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.058
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
Cadd	Benign	20
Dann	Uncertain	0.99
DEOGEN2	Uncertain	0.49	T;T;.
Eigen	Benign	-0.086
Eigen_PC	Benign	0.072
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.91	D;D;D
M_CAP	Benign	0.036	D
MetaRNN	Uncertain	0.53	D;D;D
MetaSVM	Benign	-0.45	T
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-2.8	D;.;D
REVEL	Uncertain	0.43
Sift	Benign	0.054	T;.;T
Sift4G	Benign	0.070	T;T;T
Polyphen		0.013	B;.;.
Vest4		0.44
MutPred		0.43		Gain of catalytic residue at V1025 (P = 0.0032);.;.;
MVP		0.73
MPC		0.17
ClinPred		0.98	D
GERP RS		4.9
Varity_R		0.35
gMVP		0.28

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

Other links and lift over

dbSNP: rs1555241837; hg19: chr12-105556554;