chr2-74490124-C-A

Variant names:

• chr2-74490124-C-A
• NM_022492.6:c.229C>A

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.229C>A​(p.His77Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000691 in 1,448,134 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: TTC31 NM_022492.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.980
• 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=0.24898612).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022492.6. 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.229C>A	p.His77Asn	missense	Exon 3 of 13	NP_071937.4	Q49AM3-1
	TTC31	NM_001376129.1		c.229C>A	p.His77Asn	missense	Exon 3 of 13	NP_001363058.1
	TTC31	NM_001376130.1		c.229C>A	p.His77Asn	missense	Exon 3 of 13	NP_001363059.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTC31	ENST00000233623.11	TSL:1 MANE Select	c.229C>A	p.His77Asn	missense	Exon 3 of 13	ENSP00000233623.6	Q49AM3-1
	TTC31	ENST00000410003.5	TSL:1	c.229C>A	p.His77Asn	missense	Exon 3 of 10	ENSP00000387213.1	G5E9H3
	TTC31	ENST00000442235.6	TSL:1	c.229C>A	p.His77Asn	missense	Exon 3 of 9	ENSP00000416823.3	Q49AM3-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.91e-7 AC: 1 AN: 1448134 Hom.: 0 Cov.: 35 AF XY: 0.00000139 AC XY: 1 AN XY: 719100

African (AFR) AF: 0.00 AC: 0 AN: 33296

American (AMR) AF: 0.00 AC: 0 AN: 41638

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25774

East Asian (EAS) AF: 0.00 AC: 0 AN: 39182

South Asian (SAS) AF: 0.00 AC: 0 AN: 84764

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52518

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1105382

Other (OTH) AF: 0.0000167 AC: 1 AN: 59832

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0083	T
Eigen	Benign	0.0046
Eigen_PC	Benign	0.074
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	2.0	M
PhyloP100		0.98
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.085
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.026	D
Polyphen		0.42	B
Vest4		0.53
MutPred		0.33		Loss of helix (P = 0.028)
MVP		0.60
MPC		0.19
ClinPred		0.92	D
GERP RS		3.0
Varity_R		0.20
gMVP		0.26
Mutation Taster		=92/8	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

hg19: chr2-74717251;