10-28533812-C-T

Variant names:

• chr10-28533812-C-T
• rs148938334
• NM_016628.5:c.42-186C>T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_016628.5(WAC):​c.42-186C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.012 in 989,418 control chromosomes in the GnomAD database, including 103 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0091 (8 hom., cov: 32)
  • Exomes 𝑓: 0.013 (95 hom.)
• Consequence: WAC NM_016628.5 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0430
• 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: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 10-28533812-C-T is Benign according to our data. Variant chr10-28533812-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1199167.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 1390 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.42-186C>T		intron	N/A	NP_057712.2
	WAC	NM_100264.3		c.-94-186C>T		intron	N/A	NP_567822.1	Q9BTA9-2
	WAC	NM_100486.4		c.42-186C>T		intron	N/A	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.42-186C>T		intron	N/A	ENSP00000346986.4	Q9BTA9-1
	WAC	ENST00000375664.8	TSL:1	c.-94-186C>T		intron	N/A	ENSP00000364816.3	Q9BTA9-2
	WAC	ENST00000428935.6	TSL:2	c.-94-186C>T		intron	N/A	ENSP00000399706.3	A0A0A0MSR1

Frequencies

GnomAD3 genomes AF: 0.00916 AC: 1391 AN: 151886 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.00302

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0110

Gnomad ASJ AF: 0.0176

Gnomad EAS AF: 0.000195

Gnomad SAS AF: 0.00270

Gnomad FIN AF: 0.00208

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.0145

Gnomad OTH AF: 0.00671

GnomAD4 exome AF: 0.0125 AC: 10506 AN: 837428 Hom.: 95 Cov.: 11 AF XY: 0.0123 AC XY: 5205 AN XY: 423828

African (AFR) AF: 0.00262 AC: 43 AN: 16424

American (AMR) AF: 0.00879 AC: 181 AN: 20598

Ashkenazi Jewish (ASJ) AF: 0.0188 AC: 300 AN: 15980

East Asian (EAS) AF: 0.00 AC: 0 AN: 28770

South Asian (SAS) AF: 0.00544 AC: 303 AN: 55700

European-Finnish (FIN) AF: 0.00292 AC: 122 AN: 41824

Middle Eastern (MID) AF: 0.00769 AC: 21 AN: 2730

European-Non Finnish (NFE) AF: 0.0147 AC: 9049 AN: 617072

Other (OTH) AF: 0.0127 AC: 487 AN: 38330

GnomAD4 genome AF: 0.00915 AC: 1390 AN: 151990 Hom.: 8 Cov.: 32 AF XY: 0.00879 AC XY: 653 AN XY: 74282

African (AFR) AF: 0.00299 AC: 124 AN: 41490

American (AMR) AF: 0.0110 AC: 168 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0176 AC: 61 AN: 3464

East Asian (EAS) AF: 0.000195 AC: 1 AN: 5118

South Asian (SAS) AF: 0.00270 AC: 13 AN: 4812

European-Finnish (FIN) AF: 0.00208 AC: 22 AN: 10592

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.0145 AC: 986 AN: 67918

Other (OTH) AF: 0.00664 AC: 14 AN: 2108

Alfa AF: 0.00927 Hom.: 7

Bravo AF: 0.00992

Asia WGS AF: 0.00202 AC: 7 AN: 3470

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	8.0
DANN	Benign	0.82
PhyloP100		0.043
PromoterAI		0.068	Neutral
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.4
Mutation Taster		=100/0	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: rs148938334; hg19: chr10-28822741;