2-47060786-C-A

Variant names:

• chr2-47060786-C-A
• rs140166160
• NM_020458.4:c.2170C>A

Variant summary

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

The NM_020458.4(TTC7A):​c.2170C>A​(p.Gln724Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00688 in 1,609,952 control chromosomes in the GnomAD database, including 56 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. Q724Q) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0045 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0071 (52 hom.)
• Consequence: TTC7A NM_020458.4 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.22
• Publications: 12 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004559338).
• BP6: Variant 2-47060786-C-A is Benign according to our data. Variant chr2-47060786-C-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 528469.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0045 (686/152336) while in subpopulation NFE AF = 0.00723 (492/68026). AF 95% confidence interval is 0.0067. There are 4 homozygotes in GnomAd4. There are 341 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 4 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTC7A	NM_020458.4	MANE Select	c.2170C>A	p.Gln724Lys	missense	Exon 19 of 20	NP_065191.2
	TTC7A	NM_001288951.2		c.2242C>A	p.Gln748Lys	missense	Exon 20 of 21	NP_001275880.1
	TTC7A	NM_001288953.2		c.2068C>A	p.Gln690Lys	missense	Exon 20 of 21	NP_001275882.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTC7A	ENST00000319190.11	TSL:2 MANE Select	c.2170C>A	p.Gln724Lys	missense	Exon 19 of 20	ENSP00000316699.5
	TTC7A	ENST00000394850.6	TSL:1	c.2242C>A	p.Gln748Lys	missense	Exon 20 of 21	ENSP00000378320.2
	TTC7A	ENST00000409825.5	TSL:1	n.*1919C>A		non_coding_transcript_exon	Exon 20 of 21	ENSP00000386521.1

Frequencies

GnomAD3 genomes AF: 0.00451 AC: 686 AN: 152218 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00181

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00510

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00559

Gnomad FIN AF: 0.000565

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00723

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00499 AC: 1246 AN: 249682 AF XY: 0.00549

Gnomad AFR exome AF: 0.00166

Gnomad AMR exome AF: 0.00381

Gnomad ASJ exome AF: 0.00152

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000836

Gnomad NFE exome AF: 0.00733

Gnomad OTH exome AF: 0.00459

GnomAD4 exome AF: 0.00713 AC: 10396 AN: 1457616 Hom.: 52 Cov.: 31 AF XY: 0.00706 AC XY: 5111 AN XY: 724414

African (AFR) AF: 0.00117 AC: 39 AN: 33422

American (AMR) AF: 0.00366 AC: 163 AN: 44566

Ashkenazi Jewish (ASJ) AF: 0.00166 AC: 43 AN: 25908

East Asian (EAS) AF: 0.0000505 AC: 2 AN: 39608

South Asian (SAS) AF: 0.00687 AC: 590 AN: 85872

European-Finnish (FIN) AF: 0.000919 AC: 49 AN: 53312

Middle Eastern (MID) AF: 0.00139 AC: 8 AN: 5754

European-Non Finnish (NFE) AF: 0.00821 AC: 9109 AN: 1108978

Other (OTH) AF: 0.00653 AC: 393 AN: 60196

GnomAD4 genome AF: 0.00450 AC: 686 AN: 152336 Hom.: 4 Cov.: 32 AF XY: 0.00458 AC XY: 341 AN XY: 74494

African (AFR) AF: 0.00180 AC: 75 AN: 41578

American (AMR) AF: 0.00510 AC: 78 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00559 AC: 27 AN: 4828

European-Finnish (FIN) AF: 0.000565 AC: 6 AN: 10624

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

European-Non Finnish (NFE) AF: 0.00723 AC: 492 AN: 68026

Other (OTH) AF: 0.00284 AC: 6 AN: 2114

Alfa AF: 0.00616 Hom.: 7

Bravo AF: 0.00457

TwinsUK AF: 0.0102 AC: 38

ALSPAC AF: 0.00986 AC: 38

ESP6500AA AF: 0.00182 AC: 8

ESP6500EA AF: 0.00663 AC: 57

ExAC AF: 0.00482 AC: 585

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.00709

EpiControl AF: 0.00706

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

TTC7A: BP4, BS2

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Multiple gastrointestinal atresias Benign:1

Feb 01, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	22
DANN	Benign	0.93
DEOGEN2	Benign	0.069	T
Eigen	Benign	0.039
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.0046	T
MetaSVM	Benign	-0.64	T
MutationAssessor	Benign	1.4	L
PhyloP100		1.2
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.15
Sift	Benign	0.20	T
Sift4G	Benign	0.61	T
Polyphen		0.12	B
Vest4		0.26
MVP		0.81
MPC		0.078
ClinPred		0.0082	T
GERP RS		5.8
Varity_R		0.11
gMVP		0.40
Mutation Taster		=98/2	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: rs140166160; hg19: chr2-47287925; COSMIC: COSV99766319; COSMIC: COSV99766319;