rs763226630

Variant names:

• chr10-28533531-C-G
• rs763226630
• NM_016628.5:c.-49C>G

Your query was ambiguous. Multiple possible variants found:

• chr10-28533531-C-G
• chr10-28533531-C-T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_016628.5(WAC):​c.-49C>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000391 in 1,229,148 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000040 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000039 (0 hom.)
• Consequence: WAC NM_016628.5 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.701
• 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, G2P, Orphanet

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 10-28533531-C-G is Benign according to our data. Variant chr10-28533531-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1188283.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 6 AD gene.

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.-49C>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 14	NP_057712.2
	WAC	NM_016628.5	MANE Select	c.-49C>G		5_prime_UTR	Exon 1 of 14	NP_057712.2
	WAC	NM_100486.4		c.-49C>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 13	NP_567823.1	Q9BTA9-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WAC	ENST00000354911.9	TSL:1 MANE Select	c.-49C>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 14	ENSP00000346986.4	Q9BTA9-1
	WAC	ENST00000651885.1		c.-49C>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 5	ENSP00000498678.1	A0A494C0S5
	WAC	ENST00000354911.9	TSL:1 MANE Select	c.-49C>G		5_prime_UTR	Exon 1 of 14	ENSP00000346986.4	Q9BTA9-1

Frequencies

GnomAD3 genomes AF: 0.0000403 AC: 6 AN: 148886 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000133

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: 0.0000449

Gnomad OTH AF: 0.000488

GnomAD2 exomes AF: 0.000150 AC: 26 AN: 173206 AF XY: 0.000163

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000685

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000729

Gnomad OTH exome AF: 0.00187

GnomAD4 exome AF: 0.0000389 AC: 42 AN: 1080262 Hom.: 0 Cov.: 27 AF XY: 0.0000377 AC XY: 20 AN XY: 530236

African (AFR) AF: 0.00 AC: 0 AN: 21824

American (AMR) AF: 0.000704 AC: 16 AN: 22720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14204

East Asian (EAS) AF: 0.00 AC: 0 AN: 15946

South Asian (SAS) AF: 0.00 AC: 0 AN: 43096

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28224

Middle Eastern (MID) AF: 0.000496 AC: 2 AN: 4030

European-Non Finnish (NFE) AF: 0.0000224 AC: 20 AN: 891784

Other (OTH) AF: 0.000104 AC: 4 AN: 38434

GnomAD4 genome AF: 0.0000403 AC: 6 AN: 148886 Hom.: 0 Cov.: 32 AF XY: 0.0000138 AC XY: 1 AN XY: 72522

African (AFR) AF: 0.00 AC: 0 AN: 41088

American (AMR) AF: 0.000133 AC: 2 AN: 15006

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3414

East Asian (EAS) AF: 0.00 AC: 0 AN: 5106

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000449 AC: 3 AN: 66770

Other (OTH) AF: 0.000488 AC: 1 AN: 2048

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.000117

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	16
DANN	Benign	0.62
PhyloP100		0.70
PromoterAI		-0.019	Neutral

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: rs763226630; hg19: chr10-28822460;