chr2-47051835-CCC-TCT

Variant names:

• chr2-47051835-CCC-TCT
• NM_020458.4:c.2107_2109delCCCinsTCT
• TTC7A p.Pro703Ser

GermlineCancer (beta)

Variant summary

Our verdict is Uncertain significance.

+2 Uncertain · Warm

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received 2 classification points (ACMG Germline Pathogenicity v2019). PM2

The NM_020458.4(TTC7A):c.2107_2109delCCCinsTCT (p.Pro703Ser) variant causes a missense change. Note: allele frequency estimates from gnomAD may be inaccurate for this variant type (MNP or indel longer than 3 bp) due to technology limitations. The variant is absent from the gnomAD population database at sites with sufficient sequencing coverage. The affected nucleotide is highly conserved across species (PhyloP 100-way vertebrate score: 7.68). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Other variants at the same amino acid position have been reported in ClinVar (not pathogenic): p.P703= (synonymous): Likely_benign (ClinVar VariationId 4799579, 1 star); p.P703= (synonymous): Likely_benign (ClinVar VariationId 1605792, 1 star); p.P703S: Uncertain_significance (ClinVar VariationId 528458, 1 star)

• Frequency: Genomes: not found (cov: 33)
• Consequence: TTC7A NM_020458.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.67
• 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]

TTC7A Gene-Disease associations (from GenCC):

• gastrointestinal defects and immunodeficiency syndrome 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P
• multiple intestinal atresia

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, ClinGen, Ambry Genetics

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 epigenetic programing of male pronucleus. Predicted to act upstream of or within pyrimidine-containing compound catabolic process. 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, Jul 2025]

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript:

Our verdict: Uncertain_significance. The variant received 2 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	PM2Absent/extremely low in population databases		Absent from gnomAD (AR/unknown gene) — PM2; Absent from gnomAD at well-covered site (MOI: AR) (threshold 0.001) — PM2 moderate.

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_020458.4. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	TTC7A NM_020458.4	MANE Select	c.2107_2109delCCCinsTCT p.Pro703Ser	missense	N/A	Prot: NP_065191.2 UniProt:
	TTC7A NM_001288951.2		c.2179_2181delCCCinsTCT p.Pro727Ser	missense	N/A	Prot: NP_001275880.1 UniProt:
	TTC7A NM_001288953.2		c.2005_2007delCCCinsTCT p.Pro669Ser	missense	N/A	Prot: NP_001275882.1 UniProt:

TTC7A NM_020458.4

MANE Select

HGVSc / HGVSpc.2107_2109delCCCinsTCTp.Pro703Ser

Exon rankN/A

missense

Prot: NP_065191.2UniProt: Q9ULT0-1

TTC7A NM_001288951.2

HGVSc / HGVSpc.2179_2181delCCCinsTCTp.Pro727Ser

Exon rankN/A

missense

Prot: NP_001275880.1UniProt: Q9ULT0-4

TTC7A NM_001288953.2

HGVSc / HGVSpc.2005_2007delCCCinsTCTp.Pro669Ser

Exon rankN/A

missense

Prot: NP_001275882.1UniProt: G5E9G4

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	TTC7A ENST00000319190.11	TSL:2MANE Select	c.2107_2109delCCCinsTCT p.Pro703Ser	missense	N/A	Prot: ENSP00000316699.5 UniProt:
	TTC7A ENST00000394850.6	TSL:1	c.2179_2181delCCCinsTCT p.Pro727Ser	missense	N/A	Prot: ENSP00000378320.2 UniProt:
	TTC7A ENST00000409825.5	TSL:1	n.*1856_*1858delCCCinsTCT	3_prime_UTR	Exon 19 of 21	Prot: ENSP00000386521.1 UniProt:

TTC7A ENST00000319190.11

TSL:2MANE Select

HGVSc / HGVSpc.2107_2109delCCCinsTCTp.Pro703Ser

Exon rankN/A

missense

Prot: ENSP00000316699.5UniProt: Q9ULT0-1

TTC7A ENST00000394850.6

TSL:1

HGVSc / HGVSpc.2179_2181delCCCinsTCTp.Pro727Ser

Exon rankN/A

missense

Prot: ENSP00000378320.2UniProt: Q9ULT0-4

TTC7A ENST00000409825.5

TSL:1

HGVSc / HGVSpn.*1856_*1858delCCCinsTCT

Exon rankExon 19 of 21

3_prime_UTR

Prot: ENSP00000386521.1UniProt: H0Y3V7

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 2 sources Large-scale international reference populations
GnomAD3 genomes	AF:	AC:	Hom:	AN:	Cov:33
GnomAD4 genome	AF:	AC:	Hom:	AN:	Cov:33

Showing 2 sources

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
PhyloP100	Pathogenic	7.7

Showing 1 of 1 scores

Splicing Scores

No splicing scores have been computed for this variant.

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Other links and lift over

hg19: chr2-47278974;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar