rs142959785

Positions:

• chr2-47060827-G-A

Variant summary

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

The NM_020458.4(TTC7A):​c.2211G>A​(p.Ala737=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00203 in 1,613,852 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0018 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0021 (10 hom.)
• Consequence: TTC7A NM_020458.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -2.09

Genes affected

TTC7A (HGNC:19750): (tetratricopeptide repeat domain 7A) This gene encodes a protein containing tetratricopeptide repeats. Mutations in this gene disrupt intestinal development and can cause early onset inflammatory bowel disease and intestinal atresia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]

STPG4 (HGNC:26850): (sperm-tail PG-rich repeat containing 4) Predicted to enable chromatin binding activity and histone binding activity. Predicted to be involved in DNA demethylation of male pronucleus and positive regulation of DNA demethylation. Predicted to act upstream of or within C-5 methylation of cytosine. Predicted to be located in cytoplasm and nucleus. Predicted to be active in female pronucleus; germinal vesicle; and male pronucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 2-47060827-G-A is Benign according to our data. Variant chr2-47060827-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 528472.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-47060827-G-A is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=-2.09 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00177 (270/152326) while in subpopulation AMR AF= 0.00301 (46/15306). AF 95% confidence interval is 0.00231. There are 0 homozygotes in gnomad4. There are 131 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTC7A	NM_020458.4	c.2211G>A	p.Ala737=	synonymous_variant	19/20	ENST00000319190.11	NP_065191.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTC7A	ENST00000319190.11	c.2211G>A	p.Ala737=	synonymous_variant	19/20	2	NM_020458.4	ENSP00000316699	P1

Frequencies

GnomAD3 genomes AF: 0.00177 AC: 270 AN: 152208 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000675

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00301

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00243

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00164 AC: 412 AN: 251190 Hom.: 3 AF XY: 0.00174 AC XY: 236 AN XY: 135736

Gnomad AFR exome AF: 0.000246

Gnomad AMR exome AF: 0.00127

Gnomad ASJ exome AF: 0.00408

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00108

Gnomad FIN exome AF: 0.000139

Gnomad NFE exome AF: 0.00233

Gnomad OTH exome AF: 0.00359

GnomAD4 exome AF: 0.00205 AC: 3003 AN: 1461526 Hom.: 10 Cov.: 31 AF XY: 0.00209 AC XY: 1522 AN XY: 727050

Gnomad4 AFR exome AF: 0.000329

Gnomad4 AMR exome AF: 0.00127

Gnomad4 ASJ exome AF: 0.00471

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00121

Gnomad4 FIN exome AF: 0.000262

Gnomad4 NFE exome AF: 0.00227

Gnomad4 OTH exome AF: 0.00225

GnomAD4 genome AF: 0.00177 AC: 270 AN: 152326 Hom.: 0 Cov.: 32 AF XY: 0.00176 AC XY: 131 AN XY: 74480

Gnomad4 AFR AF: 0.000673

Gnomad4 AMR AF: 0.00301

Gnomad4 ASJ AF: 0.00403

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.000377

Gnomad4 NFE AF: 0.00243

Gnomad4 OTH AF: 0.00236

Alfa AF: 0.00242 Hom.: 1

Bravo AF: 0.00182

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00349

EpiControl AF: 0.00314

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2022	TTC7A: BP4, BP7 -
Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

Multiple gastrointestinal atresias Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.55
DANN	Benign	0.79

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: rs142959785; hg19: chr2-47287966;