2-32630694-C-G

Variant names:

• chr2-32630694-C-G
• rs200957498
• NM_017735.5:c.260C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_017735.5(TTC27):​c.260C>G​(p.Thr87Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000692 in 1,446,036 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T87M) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: TTC27 NM_017735.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26
• Publications: 0 publications found

Genes affected

TTC27 (HGNC:25986): (tetratricopeptide repeat domain 27)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0491634).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017735.5. 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
	TTC27	NM_017735.5	MANE Select	c.260C>G	p.Thr87Arg	missense	Exon 2 of 20	NP_060205.3
	TTC27	NM_001193509.2		c.110C>G	p.Thr37Arg	missense	Exon 2 of 20	NP_001180438.1	B4DRC7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTC27	ENST00000317907.9	TSL:1 MANE Select	c.260C>G	p.Thr87Arg	missense	Exon 2 of 20	ENSP00000313953.4	Q6P3X3
	TTC27	ENST00000934659.1		c.260C>G	p.Thr87Arg	missense	Exon 2 of 20	ENSP00000604718.1
	TTC27	ENST00000956005.1		c.260C>G	p.Thr87Arg	missense	Exon 2 of 20	ENSP00000626064.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.92e-7 AC: 1 AN: 1446036 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 719210

African (AFR) AF: 0.00 AC: 0 AN: 32356

American (AMR) AF: 0.00 AC: 0 AN: 39788

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25318

East Asian (EAS) AF: 0.00 AC: 0 AN: 39576

South Asian (SAS) AF: 0.00 AC: 0 AN: 83878

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53120

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5616

European-Non Finnish (NFE) AF: 9.04e-7 AC: 1 AN: 1106776

Other (OTH) AF: 0.00 AC: 0 AN: 59608

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	0.014
DANN	Benign	0.51
DEOGEN2	Benign	0.14	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.049	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		-1.3
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.034
Sift	Benign	0.26	T
Sift4G	Benign	0.083	T
Polyphen		0.0	B
Vest4		0.15
MutPred		0.33		Gain of phosphorylation at T86 (P = 0.0865)
MVP		0.16
MPC		0.044
ClinPred		0.12	T
GERP RS		-6.5
Varity_R		0.046
gMVP		0.35
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		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: rs200957498; hg19: chr2-32855761;