3-13819370-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_004625.4(WNT7A):c.624G>A(p.Ser208=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000312 in 1,613,260 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0017 (3 hom., cov: 32)
  • Exomes 𝑓: 0.00017 (2 hom.)
• Consequence: WNT7A NM_004625.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.10

Genes affected

WNT7A (HGNC:12786): (Wnt family member 7A) This gene is a member of the WNT gene family, which consists of structurally related genes that encode secreted signaling proteins. These proteins have been implicated in oncogenesis and in several developmental processes, including regulation of cell fate and patterning during embryogenesis. This gene is involved in the development of the anterior-posterior axis in the female reproductive tract, and also plays a critical role in uterine smooth muscle pattering and maintenance of adult uterine function. Mutations in this gene are associated with Fuhrmann and Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndromes. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 3-13819370-C-T is Benign according to our data. Variant chr3-13819370-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 743183.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.1 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00169 (258/152278) while in subpopulation AFR AF= 0.00604 (251/41546). AF 95% confidence interval is 0.00543. There are 3 homozygotes in gnomad4. There are 118 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WNT7A	NM_004625.4	c.624G>A	p.Ser208=	synonymous_variant	4/4	ENST00000285018.5
WNT7A	XM_011534091.3	c.423G>A	p.Ser141=	synonymous_variant	5/5
WNT7A	XM_047448863.1	c.423G>A	p.Ser141=	synonymous_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WNT7A	ENST00000285018.5	c.624G>A	p.Ser208=	synonymous_variant	4/4	1	NM_004625.4	P1

Frequencies

GnomAD3 genomes AF: 0.00170 AC: 258 AN: 152160 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00606

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

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: 0.0000147

Gnomad OTH AF: 0.000956

GnomAD3 exomes AF: 0.000392 AC: 98 AN: 250286 Hom.: 0 AF XY: 0.000185 AC XY: 25 AN XY: 135208

Gnomad AFR exome AF: 0.00560

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000329

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000883

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000168 AC: 245 AN: 1460982 Hom.: 2 Cov.: 31 AF XY: 0.000131 AC XY: 95 AN XY: 726756

Gnomad4 AFR exome AF: 0.00660

Gnomad4 AMR exome AF: 0.000112

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000349

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.000215

GnomAD4 genome AF: 0.00169 AC: 258 AN: 152278 Hom.: 3 Cov.: 32 AF XY: 0.00158 AC XY: 118 AN XY: 74468

Gnomad4 AFR AF: 0.00604

Gnomad4 AMR AF: 0.000261

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.000946

Alfa AF: 0.000884 Hom.: 0

Bravo AF: 0.00187

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Nov 28, 2022	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 11, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
Cadd	Benign	2.5
Dann	Benign	0.81

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

LitVar

Other links and lift over

dbSNP: rs143102670; hg19: chr3-13860867;