3-13818812-G-A

Variant names:

• chr3-13818812-G-A
• rs189888897
• NM_004625.4:c.*132C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_004625.4(WNT7A):​c.*132C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00122 in 1,369,774 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0062 (9 hom., cov: 32)
  • Exomes 𝑓: 0.00060 (3 hom.)
• Consequence: WNT7A NM_004625.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.515
• Publications: 0 publications found

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]

WNT7A Gene-Disease associations (from GenCC):

• Fuhrmann syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet
• phocomelia, Schinzel type

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 3-13818812-G-A is Benign according to our data. Variant chr3-13818812-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1212528.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00619 (942/152102) while in subpopulation AFR AF = 0.0212 (880/41460). AF 95% confidence interval is 0.0201. There are 9 homozygotes in GnomAd4. There are 453 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNT7A	NM_004625.4	c.*132C>T		3_prime_UTR_variant	Exon 4 of 4	ENST00000285018.5	NP_004616.2
WNT7A	XM_011534091.3	c.*132C>T		3_prime_UTR_variant	Exon 5 of 5		XP_011532393.1
WNT7A	XM_047448863.1	c.*132C>T		3_prime_UTR_variant	Exon 4 of 4		XP_047304819.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WNT7A	ENST00000285018.5	c.*132C>T		3_prime_UTR_variant	Exon 4 of 4	1	NM_004625.4	ENSP00000285018.4

Frequencies

GnomAD3 genomes AF: 0.00620 AC: 942 AN: 151986 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.0213

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00341

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: 0.0000294

Gnomad OTH AF: 0.00384

GnomAD4 exome AF: 0.000600 AC: 730 AN: 1217672 Hom.: 3 Cov.: 19 AF XY: 0.000541 AC XY: 320 AN XY: 591594

African (AFR) AF: 0.0213 AC: 574 AN: 26928

American (AMR) AF: 0.00213 AC: 41 AN: 19286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18396

East Asian (EAS) AF: 0.00 AC: 0 AN: 34310

South Asian (SAS) AF: 0.0000679 AC: 4 AN: 58914

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32222

Middle Eastern (MID) AF: 0.00173 AC: 6 AN: 3478

European-Non Finnish (NFE) AF: 0.0000349 AC: 34 AN: 972974

Other (OTH) AF: 0.00139 AC: 71 AN: 51164

GnomAD4 genome AF: 0.00619 AC: 942 AN: 152102 Hom.: 9 Cov.: 32 AF XY: 0.00609 AC XY: 453 AN XY: 74354

African (AFR) AF: 0.0212 AC: 880 AN: 41460

American (AMR) AF: 0.00340 AC: 52 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10584

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68014

Other (OTH) AF: 0.00380 AC: 8 AN: 2106

Alfa AF: 0.00492 Hom.: 0

Bravo AF: 0.00741

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 23, 2020

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	11
DANN	Benign	0.66
PhyloP100		0.52
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: rs189888897; hg19: chr3-13860309;