rs587777411

Variant names:

• chr12-105160144-C-A
• NM_015275.3:c.3056C>A

Your query was ambiguous. Multiple possible variants found:

• chr12-105160144-C-A
• chr12-105160144-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_015275.3(WASHC4):​c.3056C>A​(p.Pro1019His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,920 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: WASHC4 NM_015275.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.74

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.877

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WASHC4	NM_015275.3	c.3056C>A	p.Pro1019His	missense_variant	Exon 29 of 33	ENST00000332180.10	NP_056090.1
WASHC4	NM_001293640.2	c.3059C>A	p.Pro1020His	missense_variant	Exon 29 of 33		NP_001280569.1
WASHC4	XM_011538073.4	c.2921C>A	p.Pro974His	missense_variant	Exon 28 of 32		XP_011536375.1
WASHC4	XM_011538074.3	c.2492C>A	p.Pro831His	missense_variant	Exon 23 of 27		XP_011536376.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WASHC4	ENST00000332180.10	c.3056C>A	p.Pro1019His	missense_variant	Exon 29 of 33	1	NM_015275.3	ENSP00000328062.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1460920 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726838

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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.43	D
BayesDel_noAF	Pathogenic	0.38
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.73	D;T;.
Eigen	Pathogenic	0.84
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.97	D;D;D
M_CAP	Uncertain	0.15	D
MetaRNN	Pathogenic	0.88	D;D;D
MetaSVM	Uncertain	0.51	D
PrimateAI	Pathogenic	0.86	D
PROVEAN	Pathogenic	-6.7	D;.;D
REVEL	Pathogenic	0.90
Sift	Uncertain	0.0010	D;.;D
Sift4G	Pathogenic	0.0010	D;D;D
Polyphen		1.0	D;.;.
Vest4		0.95
MutPred		0.60		Gain of catalytic residue at T1021 (P = 0);.;.;
MVP		0.89
MPC		0.77
ClinPred		1.0	D
GERP RS		4.8
Varity_R		0.78
gMVP		0.71

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-105553922;