rs58422168

Variant names:

• chr2-47073806-C-T
• rs58422168
• NM_020458.4:c.2460C>T

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.2460C>T​(p.Gly820Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00339 in 1,613,614 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0026 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0035 (19 hom.)
• Consequence: TTC7A NM_020458.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -3.85
• 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]

ENSG00000273269 (HGNC:):

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=-0.6).
• BP6: Variant 2-47073806-C-T is Benign according to our data. Variant chr2-47073806-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 458797.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.85 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00255 (389/152266) while in subpopulation NFE AF = 0.00431 (293/68022). AF 95% confidence interval is 0.0039. There are 0 homozygotes in GnomAd4. There are 184 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 19 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.2460C>T	p.Gly820Gly	synonymous	Exon 20 of 20	NP_065191.2	Q9ULT0-1
	TTC7A	NM_001288951.2		c.2532C>T	p.Gly844Gly	synonymous	Exon 21 of 21	NP_001275880.1	Q9ULT0-4
	TTC7A	NM_001288953.2		c.2358C>T	p.Gly786Gly	synonymous	Exon 21 of 21	NP_001275882.1	G5E9G4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTC7A	ENST00000319190.11	TSL:2 MANE Select	c.2460C>T	p.Gly820Gly	synonymous	Exon 20 of 20	ENSP00000316699.5	Q9ULT0-1
	TTC7A	ENST00000394850.6	TSL:1	c.2532C>T	p.Gly844Gly	synonymous	Exon 21 of 21	ENSP00000378320.2	Q9ULT0-4
	TTC7A	ENST00000409825.5	TSL:1	n.*2209C>T		non_coding_transcript_exon	Exon 21 of 21	ENSP00000386521.1	H0Y3V7

Frequencies

GnomAD3 genomes AF: 0.00256 AC: 389 AN: 152148 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000797

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00124

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00405

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00431

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.00227 AC: 568 AN: 250590 AF XY: 0.00217

Gnomad AFR exome AF: 0.000433

Gnomad AMR exome AF: 0.000260

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000545

Gnomad FIN exome AF: 0.00421

Gnomad NFE exome AF: 0.00397

Gnomad OTH exome AF: 0.00180

GnomAD4 exome AF: 0.00348 AC: 5086 AN: 1461348 Hom.: 19 Cov.: 31 AF XY: 0.00338 AC XY: 2456 AN XY: 727008

African (AFR) AF: 0.000508 AC: 17 AN: 33478

American (AMR) AF: 0.000268 AC: 12 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39696

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86256

European-Finnish (FIN) AF: 0.00409 AC: 217 AN: 52996

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5752

European-Non Finnish (NFE) AF: 0.00424 AC: 4720 AN: 1111950

Other (OTH) AF: 0.00190 AC: 115 AN: 60386

GnomAD4 genome AF: 0.00255 AC: 389 AN: 152266 Hom.: 0 Cov.: 33 AF XY: 0.00247 AC XY: 184 AN XY: 74452

African (AFR) AF: 0.000794 AC: 33 AN: 41546

American (AMR) AF: 0.00124 AC: 19 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00405 AC: 43 AN: 10612

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

European-Non Finnish (NFE) AF: 0.00431 AC: 293 AN: 68022

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.00317 Hom.: 0

Bravo AF: 0.00193

EpiCase AF: 0.00284

EpiControl AF: 0.00362

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Multiple gastrointestinal atresias (1)
-	-	1	TTC7A-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	4.5
DANN	Benign	0.89
PhyloP100		-3.8
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs58422168; hg19: chr2-47300945; COSMIC: COSV55412938; COSMIC: COSV55412938;