chr2-74483342-T-G

Variant names:

• chr2-74483342-T-G
• rs202176729
• NM_022492.6:c.61T>G

Variant summary

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

The NM_022492.6(TTC31):​c.61T>G​(p.Cys21Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,214 control chromosomes in the GnomAD database, with no homozygous occurrence. 14/22 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. C21R) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
• Consequence: TTC31 NM_022492.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.12
• Publications: 0 publications found

Genes affected

TTC31 (HGNC:25759): (tetratricopeptide repeat domain 31)

CCDC142 (HGNC:25889): (coiled-coil domain containing 142)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC31	NM_022492.6	c.61T>G	p.Cys21Gly	missense_variant	Exon 2 of 13	ENST00000233623.11	NP_071937.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTC31	ENST00000233623.11	c.61T>G	p.Cys21Gly	missense_variant	Exon 2 of 13	1	NM_022492.6	ENSP00000233623.6

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152214 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152214 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74360

African (AFR) AF: 0.0000241 AC: 1 AN: 41458

American (AMR) AF: 0.00 AC: 0 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	22
DANN	Benign	0.95
DEOGEN2	Benign	0.015	.;.;T
Eigen	Benign	0.10
Eigen_PC	Benign	0.064
FATHMM_MKL	Benign	0.34	N
LIST_S2	Benign	0.66	T;T;T
M_CAP	Benign	0.0064	T
MetaRNN	Uncertain	0.57	D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	2.0	M;.;M
PhyloP100		1.1
PrimateAI	Benign	0.32	T
PROVEAN	Pathogenic	-5.7	.;D;N
REVEL	Benign	0.066
Sift	Pathogenic	0.0	.;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		0.92	.;.;P
Vest4		0.54
MutPred		0.47		Gain of disorder (P = 0.0254);Gain of disorder (P = 0.0254);Gain of disorder (P = 0.0254);
MVP		0.66
MPC		0.52
ClinPred		1.0	D
GERP RS		3.1
PromoterAI		0.28	Neutral
Varity_R		0.91
gMVP		0.33
Mutation Taster		=96/4	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: rs202176729; hg19: chr2-74710469;