chr12-105152393-A-C

Variant names:

• chr12-105152393-A-C
• rs202242349
• NM_015275.3:c.2700A>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_015275.3(WASHC4):​c.2700A>C​(p.Gly900Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00249 in 1,607,930 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0015 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0026 (8 hom.)
• Consequence: WASHC4 NM_015275.3 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 3.35
• Publications: 2 publications found

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]

WASHC4 Gene-Disease associations (from GenCC):

• autosomal recessive non-syndromic intellectual disability

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• intellectual disability, autosomal recessive 43

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics
• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 12-105152393-A-C is Benign according to our data. Variant chr12-105152393-A-C is described in ClinVar as Likely_benign. ClinVar VariationId is 435582.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=3.35 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00146 (223/152288) while in subpopulation NFE AF = 0.00243 (165/68010). AF 95% confidence interval is 0.00212. There are 0 homozygotes in GnomAd4. There are 110 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 8 AR,Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015275.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WASHC4	NM_015275.3	MANE Select	c.2700A>C	p.Gly900Gly	synonymous	Exon 26 of 33	NP_056090.1
	WASHC4	NM_001293640.2		c.2703A>C	p.Gly901Gly	synonymous	Exon 26 of 33	NP_001280569.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WASHC4	ENST00000332180.10	TSL:1 MANE Select	c.2700A>C	p.Gly900Gly	synonymous	Exon 26 of 33	ENSP00000328062.6
	WASHC4	ENST00000620430.5	TSL:1	c.2703A>C	p.Gly901Gly	synonymous	Exon 26 of 33	ENSP00000484713.1
	WASHC4	ENST00000550053.5	TSL:5	n.*2142A>C		non_coding_transcript_exon	Exon 26 of 33	ENSP00000448966.1

Frequencies

GnomAD3 genomes AF: 0.00147 AC: 223 AN: 152170 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000676

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000982

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00132

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00243

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.00144 AC: 359 AN: 249268 AF XY: 0.00148

Gnomad AFR exome AF: 0.000904

Gnomad AMR exome AF: 0.000551

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00204

Gnomad NFE exome AF: 0.00239

Gnomad OTH exome AF: 0.00132

GnomAD4 exome AF: 0.00260 AC: 3788 AN: 1455642 Hom.: 8 Cov.: 27 AF XY: 0.00246 AC XY: 1785 AN XY: 724684

African (AFR) AF: 0.000780 AC: 26 AN: 33320

American (AMR) AF: 0.000559 AC: 25 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26078

East Asian (EAS) AF: 0.00 AC: 0 AN: 39622

South Asian (SAS) AF: 0.0000581 AC: 5 AN: 86126

European-Finnish (FIN) AF: 0.00169 AC: 90 AN: 53410

Middle Eastern (MID) AF: 0.00122 AC: 7 AN: 5756

European-Non Finnish (NFE) AF: 0.00315 AC: 3489 AN: 1106436

Other (OTH) AF: 0.00243 AC: 146 AN: 60178

GnomAD4 genome AF: 0.00146 AC: 223 AN: 152288 Hom.: 0 Cov.: 33 AF XY: 0.00148 AC XY: 110 AN XY: 74476

African (AFR) AF: 0.000674 AC: 28 AN: 41562

American (AMR) AF: 0.000980 AC: 15 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00132 AC: 14 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00243 AC: 165 AN: 68010

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.00213 Hom.: 0

Bravo AF: 0.00155

EpiCase AF: 0.00376

EpiControl AF: 0.00261

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Jul 06, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Sep 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

WASHC4: BP4, BS2

not specified Benign:1

Dec 02, 2016

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	8.7
DANN	Benign	0.74
PhyloP100		3.3
PromoterAI		0.036	Neutral
Mutation Taster		=100/0	polymorphism

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: rs202242349; hg19: chr12-105546171;