NM_001378090.1:c.1381G>C

Variant names:

• chr9-14824-C-G
• rs772931051
• NM_001378090.1:c.1381G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001378090.1(WASHC1):​c.1381G>C​(p.Asp461His) variant causes a missense change. The variant allele was found at a frequency of 0.000132 in 143,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00013 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000030 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: WASHC1 NM_001378090.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.57
• Publications: 0 publications found

Genes affected

WASHC1 (HGNC:24361): (WASH complex subunit 1) Enables alpha-tubulin binding activity and ubiquitin protein ligase binding activity. Involved in several processes, including Arp2/3 complex-mediated actin nucleation; endosomal transport; and positive regulation of pseudopodium assembly. Located in early endosome. Part of WASH complex. Colocalizes with exocyst. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.1664063).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378090.1. 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
	WASHC1	NM_001378090.1	MANE Select	c.1381G>C	p.Asp461His	missense	Exon 11 of 11	NP_001365019.1	A8K0Z3
	WASHC1	NM_182905.6		c.1381G>C	p.Asp461His	missense	Exon 11 of 11	NP_878908.4	A8K0Z3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WASHC1	ENST00000696149.1	MANE Select	c.1381G>C	p.Asp461His	missense	Exon 11 of 11	ENSP00000512441.1	A8K0Z3
	WASHC1	ENST00000442898.5	TSL:2	c.1381G>C	p.Asp461His	missense	Exon 11 of 11	ENSP00000485627.1	A8K0Z3

Frequencies

GnomAD3 genomes AF: 0.000132 AC: 19 AN: 143884 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000513

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

GnomAD2 exomes AF: 0.0000334 AC: 7 AN: 209524 AF XY: 0.0000349

Gnomad AFR exome AF: 0.000707

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS 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: 0.0000297 AC: 41 AN: 1382064 Hom.: 0 Cov.: 39 AF XY: 0.0000247 AC XY: 17 AN XY: 689182

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

African (AFR) AF: 0.00109 AC: 33 AN: 30206

American (AMR) AF: 0.00 AC: 0 AN: 43448

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24728

East Asian (EAS) AF: 0.00 AC: 0 AN: 39170

South Asian (SAS) AF: 0.00 AC: 0 AN: 83178

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50878

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3900

European-Non Finnish (NFE) AF: 9.53e-7 AC: 1 AN: 1049482

Other (OTH) AF: 0.000123 AC: 7 AN: 57074

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000000971516), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000132 AC: 19 AN: 143884 Hom.: 0 Cov.: 31 AF XY: 0.000128 AC XY: 9 AN XY: 70100

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

African (AFR) AF: 0.000513 AC: 19 AN: 37012

American (AMR) AF: 0.00 AC: 0 AN: 14668

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3346

East Asian (EAS) AF: 0.00 AC: 0 AN: 5140

South Asian (SAS) AF: 0.00 AC: 0 AN: 4594

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10260

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 306

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 65784

Other (OTH) AF: 0.00 AC: 0 AN: 1950

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0000971 Hom.: 0

ExAC AF: 0.0000634 AC: 7

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Uncertain	23
DANN	Benign	0.89
DEOGEN2	Benign	0.15	T
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.92	D
MetaRNN	Benign	0.17	T
MutationAssessor	Pathogenic	3.2	M
PhyloP100		4.6
PrimateAI	Uncertain	0.67	T
Sift4G	Uncertain	0.0040	D
Polyphen		0.98	D
Vest4		0.32
MVP		0.32
GERP RS		1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.063
gMVP		0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs772931051; hg19: chr9-14824;