2-74490040-C-G

Variant names:

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

Variant summary

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

The NM_001376140.1(TTC31):​c.-288C>G variant causes a 5 prime UTR premature start codon gain 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TTC31 NM_001376140.1 5_prime_UTR_premature_start_codon_gain
• 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).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001376140.1. 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
	TTC31	NM_022492.6	MANE Select	c.145C>G	p.Leu49Val	missense	Exon 3 of 13	NP_071937.4	Q49AM3-1
	TTC31	NM_001376140.1		c.-288C>G		5_prime_UTR_premature_start_codon_gain	Exon 2 of 12	NP_001363069.1
	TTC31	NM_001376129.1		c.145C>G	p.Leu49Val	missense	Exon 3 of 13	NP_001363058.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTC31	ENST00000233623.11	TSL:1 MANE Select	c.145C>G	p.Leu49Val	missense	Exon 3 of 13	ENSP00000233623.6	Q49AM3-1
	TTC31	ENST00000410003.5	TSL:1	c.145C>G	p.Leu49Val	missense	Exon 3 of 10	ENSP00000387213.1	G5E9H3
	TTC31	ENST00000442235.6	TSL:1	c.145C>G	p.Leu49Val	missense	Exon 3 of 9	ENSP00000416823.3	Q49AM3-2

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 v4.9

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
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		1.7
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.045
Sift	Uncertain	0.023	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.88	P
Vest4		0.36
MutPred		0.24		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;