rs2063526159

Variant names:

• chr2-32628333-C-A
• rs2063526159
• NM_017735.5:c.41C>A

Your query was ambiguous. Multiple possible variants found:

• chr2-32628333-C-A
• chr2-32628333-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017735.5(TTC27):​c.41C>A​(p.Thr14Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000000687 in 1,455,712 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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. T14I) has been classified as Uncertain significance.

• 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: 3.71
• Publications: 0 publications found

Genes affected

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

ENSG00000295153 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22700316).

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.41C>A	p.Thr14Asn	missense	Exon 1 of 20	NP_060205.3
	TTC27	NM_001193509.2		c.-63+200C>A		intron	N/A	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.41C>A	p.Thr14Asn	missense	Exon 1 of 20	ENSP00000313953.4	Q6P3X3
	TTC27	ENST00000934659.1		c.41C>A	p.Thr14Asn	missense	Exon 1 of 20	ENSP00000604718.1
	TTC27	ENST00000956005.1		c.41C>A	p.Thr14Asn	missense	Exon 1 of 20	ENSP00000626064.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455712 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 723402

African (AFR) AF: 0.00 AC: 0 AN: 33400

American (AMR) AF: 0.00 AC: 0 AN: 43624

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25772

East Asian (EAS) AF: 0.00 AC: 0 AN: 39384

South Asian (SAS) AF: 0.00 AC: 0 AN: 84412

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53068

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1110132

Other (OTH) AF: 0.00 AC: 0 AN: 60172

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.039	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.090	T
Eigen	Benign	0.16
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.69	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		3.7
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.27	N
REVEL	Benign	0.10
Sift	Benign	0.037	D
Sift4G	Benign	0.13	T
Polyphen		0.38	B
Vest4		0.30
MutPred		0.21		Loss of phosphorylation at T14 (P = 0.0486)
MVP		0.69
MPC		0.096
ClinPred		0.78	D
GERP RS		5.3
PromoterAI		0.022	Neutral
Varity_R		0.12
gMVP		0.37
Mutation Taster		=90/10	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: rs2063526159; hg19: chr2-32853400;