NM_016628.5:c.59G>T

Variant names:

• chr10-28534015-G-T
• NM_016628.5:c.59G>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_016628.5(WAC):​c.59G>T​(p.Gly20Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000069 in 1,449,260 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: WAC NM_016628.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.81

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WAC	NM_016628.5	c.59G>T	p.Gly20Val	missense_variant	Exon 2 of 14	ENST00000354911.9	NP_057712.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WAC	ENST00000354911.9	c.59G>T	p.Gly20Val	missense_variant	Exon 2 of 14	1	NM_016628.5	ENSP00000346986.4
WAC	ENST00000651885.1	c.59G>T	p.Gly20Val	missense_variant	Exon 2 of 5			ENSP00000498678.1
WAC	ENST00000428935	c.-77G>T		5_prime_UTR_variant	Exon 2 of 8	2		ENSP00000399706.3
WAC	ENST00000651598	c.-95G>T		5_prime_UTR_variant	Exon 2 of 6			ENSP00000498480.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.90e-7 AC: 1 AN: 1449260 Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1 AN XY: 721062

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.04e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.053	T
BayesDel_noAF	Benign	-0.16
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.019	.;T
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Benign	0.70	D
LIST_S2	Uncertain	0.86	D;D
M_CAP	Benign	0.026	D
MetaRNN	Uncertain	0.55	D;D
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.1	L;L
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-0.83	N;N
REVEL	Benign	0.19
Sift	Uncertain	0.0030	D;.
Sift4G	Benign	0.33	T;T
Polyphen		1.0	D;D
Vest4		0.80
MutPred		0.15		Loss of catalytic residue at G20 (P = 0.0444);Loss of catalytic residue at G20 (P = 0.0444);
MVP		0.17
MPC		0.87
ClinPred		0.79	D
GERP RS		4.9
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.7
Varity_R		0.51
gMVP		0.18

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-28822944;