chr3-13854787-C-T

Variant names:

• chr3-13854787-C-T
• rs12639607
• NM_004625.4:c.315G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_004625.4(WNT7A):​c.315G>A​(p.Ala105Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 1,612,824 control chromosomes in the GnomAD database, including 34,465 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2711 hom., cov: 33)
  • Exomes 𝑓: 0.20 (31754 hom.)
• Consequence: WNT7A NM_004625.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.591
• Publications: 19 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, Orphanet, Labcorp Genetics (formerly Invitae)
• phocomelia, Schinzel type

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 3-13854787-C-T is Benign according to our data. Variant chr3-13854787-C-T is described in ClinVar as Benign. ClinVar VariationId is 1278485.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.591 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.543 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004625.4. 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
	WNT7A	NM_004625.4	MANE Select	c.315G>A	p.Ala105Ala	synonymous	Exon 3 of 4	NP_004616.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNT7A	ENST00000285018.5	TSL:1 MANE Select	c.315G>A	p.Ala105Ala	synonymous	Exon 3 of 4	ENSP00000285018.4	O00755

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24672 AN: 152112 Hom.: 2706 Cov.: 33

Gnomad AFR AF: 0.0608

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.560

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.207

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.138

GnomAD2 exomes AF: 0.208 AC: 51615 AN: 248370 AF XY: 0.205

Gnomad AFR exome AF: 0.0580

Gnomad AMR exome AF: 0.220

Gnomad ASJ exome AF: 0.120

Gnomad EAS exome AF: 0.552

Gnomad FIN exome AF: 0.208

Gnomad NFE exome AF: 0.184

Gnomad OTH exome AF: 0.183

GnomAD4 exome AF: 0.197 AC: 288312 AN: 1460594 Hom.: 31754 Cov.: 37 AF XY: 0.197 AC XY: 142849 AN XY: 726602

African (AFR) AF: 0.0542 AC: 1812 AN: 33462

American (AMR) AF: 0.213 AC: 9522 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.121 AC: 3166 AN: 26136

East Asian (EAS) AF: 0.548 AC: 21759 AN: 39698

South Asian (SAS) AF: 0.185 AC: 15972 AN: 86224

European-Finnish (FIN) AF: 0.203 AC: 10709 AN: 52718

Middle Eastern (MID) AF: 0.145 AC: 772 AN: 5316

European-Non Finnish (NFE) AF: 0.192 AC: 213015 AN: 1111996

Other (OTH) AF: 0.192 AC: 11585 AN: 60324

GnomAD4 genome AF: 0.162 AC: 24694 AN: 152230 Hom.: 2711 Cov.: 33 AF XY: 0.166 AC XY: 12325 AN XY: 74402

African (AFR) AF: 0.0608 AC: 2526 AN: 41576

American (AMR) AF: 0.180 AC: 2752 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 400 AN: 3470

East Asian (EAS) AF: 0.560 AC: 2882 AN: 5146

South Asian (SAS) AF: 0.197 AC: 949 AN: 4826

European-Finnish (FIN) AF: 0.207 AC: 2193 AN: 10584

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.184 AC: 12534 AN: 68004

Other (OTH) AF: 0.140 AC: 296 AN: 2116

Alfa AF: 0.173 Hom.: 8840

Bravo AF: 0.157

Asia WGS AF: 0.336 AC: 1169 AN: 3478

EpiCase AF: 0.177

EpiControl AF: 0.176

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	10
DANN	Benign	0.67
PhyloP100		-0.59
Mutation Taster		=91/9	polymorphism (auto)

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: rs12639607; hg19: chr3-13896284; COSMIC: COSV53197044;