rs142959785

Variant names:

• chr2-47060827-G-A
• rs142959785
• NM_020458.4:c.2211G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_020458.4(TTC7A):​c.2211G>A​(p.Ala737Ala) 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
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId is 528472.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 10 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020458.4. 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
	TTC7A	NM_020458.4	MANE Select	c.2211G>A	p.Ala737Ala	synonymous	Exon 19 of 20	NP_065191.2
	TTC7A	NM_001288951.2		c.2283G>A	p.Ala761Ala	synonymous	Exon 20 of 21	NP_001275880.1
	TTC7A	NM_001288953.2		c.2109G>A	p.Ala703Ala	synonymous	Exon 20 of 21	NP_001275882.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTC7A	ENST00000319190.11	TSL:2 MANE Select	c.2211G>A	p.Ala737Ala	synonymous	Exon 19 of 20	ENSP00000316699.5
	TTC7A	ENST00000394850.6	TSL:1	c.2283G>A	p.Ala761Ala	synonymous	Exon 20 of 21	ENSP00000378320.2
	TTC7A	ENST00000409825.5	TSL:1	n.*1960G>A		non_coding_transcript_exon	Exon 20 of 21	ENSP00000386521.1

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

GnomAD2 exomes AF: 0.00164 AC: 412 AN: 251190 AF XY: 0.00174

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 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

African (AFR) AF: 0.000329 AC: 11 AN: 33480

American (AMR) AF: 0.00127 AC: 57 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00471 AC: 123 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00121 AC: 104 AN: 86226

European-Finnish (FIN) AF: 0.000262 AC: 14 AN: 53410

Middle Eastern (MID) AF: 0.00589 AC: 34 AN: 5768

European-Non Finnish (NFE) AF: 0.00227 AC: 2524 AN: 1111734

Other (OTH) AF: 0.00225 AC: 136 AN: 60378

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

African (AFR) AF: 0.000673 AC: 28 AN: 41578

American (AMR) AF: 0.00301 AC: 46 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00403 AC: 14 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00124 AC: 6 AN: 4832

European-Finnish (FIN) AF: 0.000377 AC: 4 AN: 10620

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00243 AC: 165 AN: 68012

Other (OTH) AF: 0.00236 AC: 5 AN: 2116

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

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Multiple gastrointestinal atresias (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.55
DANN	Benign	0.79
PhyloP100		-2.1
Mutation Taster		=92/8	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: rs142959785; hg19: chr2-47287966;