NM_016628.5:c.66G>A

Variant names:

• chr10-28534022-G-A
• rs1309544145
• NM_016628.5:c.66G>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_016628.5(WAC):​c.66G>A​(p.Ser22Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000694 in 1,441,872 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S22S) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: WAC NM_016628.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.795
• Publications: 0 publications found

Genes affected

WAC (HGNC:17327): (WW domain containing adaptor with coiled-coil) The protein encoded by this gene contains a WW domain, which is a protein module found in a wide range of signaling proteins. This domain mediates protein-protein interactions and binds proteins containing short linear peptide motifs that are proline-rich or contain at least one proline. This gene product shares 94% sequence identity with the WAC protein in mouse, however, its exact function is not known. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2008]

WAC Gene-Disease associations (from GenCC):

• DeSanto-Shinawi syndrome

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• DeSanto-Shinawi syndrome due to WAC point mutation

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Illumina, Orphanet, G2P

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP7: Synonymous conserved (PhyloP=0.795 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016628.5. 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
	WAC	NM_016628.5	MANE Select	c.66G>A	p.Ser22Ser	synonymous	Exon 2 of 14	NP_057712.2
	WAC	NM_100486.4		c.66G>A	p.Ser22Ser	synonymous	Exon 2 of 13	NP_567823.1	Q9BTA9-5
	WAC	NM_100264.3		c.-70G>A		5_prime_UTR	Exon 2 of 14	NP_567822.1	Q9BTA9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WAC	ENST00000354911.9	TSL:1 MANE Select	c.66G>A	p.Ser22Ser	synonymous	Exon 2 of 14	ENSP00000346986.4	Q9BTA9-1
	WAC	ENST00000651885.1		c.66G>A	p.Ser22Ser	synonymous	Exon 2 of 5	ENSP00000498678.1	A0A494C0S5
	WAC	ENST00000375664.8	TSL:1	c.-70G>A		5_prime_UTR	Exon 2 of 14	ENSP00000364816.3	Q9BTA9-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.94e-7 AC: 1 AN: 1441872 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 717246

African (AFR) AF: 0.0000327 AC: 1 AN: 30598

American (AMR) AF: 0.00 AC: 0 AN: 42740

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25194

East Asian (EAS) AF: 0.00 AC: 0 AN: 36916

South Asian (SAS) AF: 0.00 AC: 0 AN: 85026

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53128

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5622

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1103166

Other (OTH) AF: 0.00 AC: 0 AN: 59482

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	13
DANN	Benign	0.93
PhyloP100		0.80
PromoterAI		-0.064	Neutral
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6
Mutation Taster		=299/1	polymorphism

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

Other links and lift over

dbSNP: rs1309544145; hg19: chr10-28822951;