2-32664375-C-T

Position:

• chr2-32664375-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_017735.5(TTC27):​c.713C>T​(p.Ala238Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,264 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TTC27 NM_017735.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.20

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTC27	NM_017735.5	c.713C>T	p.Ala238Val	missense_variant	6/20	ENST00000317907.9	NP_060205.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTC27	ENST00000317907.9	c.713C>T	p.Ala238Val	missense_variant	6/20	1	NM_017735.5	ENSP00000313953	P1
TTC27	ENST00000647819.1	c.713C>T	p.Ala238Val	missense_variant, NMD_transcript_variant	6/22			ENSP00000497009
TTC27	ENST00000454690.1	c.89-14481C>T		intron_variant, NMD_transcript_variant		3		ENSP00000392883

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460264 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726330

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 12, 2021

The c.713C>T (p.A238V) alteration is located in exon 6 (coding exon 6) of the TTC27 gene. This alteration results from a C to T substitution at nucleotide position 713, causing the alanine (A) at amino acid position 238 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Uncertain	0.017	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.49	T
Eigen	Benign	0.024
Eigen_PC	Benign	0.090
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.73	D
MetaSVM	Benign	-0.63	T
MutationAssessor	Uncertain	2.5	M
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-2.6	D
REVEL	Uncertain	0.32
Sift	Benign	0.053	T
Sift4G	Uncertain	0.033	D
Polyphen		0.17	B
Vest4		0.75
MutPred		0.61		Gain of helix (P = 0.2294);
MVP		0.79
MPC		0.053
ClinPred		0.89	D
GERP RS		3.8
Varity_R		0.16
gMVP		0.64

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

Publications

LitVar

Other links and lift over

dbSNP: rs1665684437; hg19: chr2-32889442;