rs774990943

Variant names:

• chr2-74490040-C-G
• rs774990943
• NM_022492.6:c.145C>G

Your query was ambiguous. Multiple possible variants found:

• chr2-74490040-C-G
• chr2-74490040-C-T

Variant summary

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

The NM_022492.6(TTC31):​c.145C>G​(p.Leu49Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 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. L49F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TTC31 NM_022492.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.73
• Publications: 0 publications found

Genes affected

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

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=0.20616987).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC31	NM_022492.6	c.145C>G	p.Leu49Val	missense_variant	Exon 3 of 13	ENST00000233623.11	NP_071937.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTC31	ENST00000233623.11	c.145C>G	p.Leu49Val	missense_variant	Exon 3 of 13	1	NM_022492.6	ENSP00000233623.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1164534 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 576028

African (AFR) AF: 0.00 AC: 0 AN: 26154

American (AMR) AF: 0.00 AC: 0 AN: 31298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18650

East Asian (EAS) AF: 0.00 AC: 0 AN: 21408

South Asian (SAS) AF: 0.00 AC: 0 AN: 77096

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32924

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4418

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 907744

Other (OTH) AF: 0.00 AC: 0 AN: 44842

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.061	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0082	.;.;T
Eigen	Benign	0.10
Eigen_PC	Benign	0.092
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.73	T;T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.21	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.0	M;.;M
PhyloP100		1.7
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-2.2	N;N;N
REVEL	Benign	0.045
Sift	Uncertain	0.023	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		0.88	.;.;P
Vest4		0.36
MutPred		0.24		Loss of helix (P = 0.1706);Loss of helix (P = 0.1706);Loss of helix (P = 0.1706);
MVP		0.61
MPC		0.22
ClinPred		0.90	D
GERP RS		2.9
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		3.7
Varity_R		0.18
gMVP		0.25
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs774990943; hg19: chr2-74717167;