NM_022492.6:c.208G>T

Variant names:

• chr2-74490103-G-T
• rs371823661
• NM_022492.6:c.208G>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.208G>T​(p.Gly70Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000694 in 1,441,422 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. G70R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: TTC31 NM_022492.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.382
• 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=0.22075266).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC31	NM_022492.6	c.208G>T	p.Gly70Trp	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.208G>T	p.Gly70Trp	missense_variant	Exon 3 of 13	1	NM_022492.6	ENSP00000233623.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.94e-7 AC: 1 AN: 1441422 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 715182

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33208

American (AMR) AF: 0.00 AC: 0 AN: 40462

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25638

East Asian (EAS) AF: 0.00 AC: 0 AN: 38806

South Asian (SAS) AF: 0.0000119 AC: 1 AN: 84010

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51970

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5742

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1101934

Other (OTH) AF: 0.00 AC: 0 AN: 59652

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.099	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.011	.;.;T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.056	N
LIST_S2	Benign	0.73	T;T;T
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.22	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L;.;L
PhyloP100		-0.38
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-3.2	.;D;N
REVEL	Benign	0.092
Sift	Uncertain	0.0060	.;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		0.59	.;.;P
Vest4		0.54
MutPred		0.42		Loss of disorder (P = 0.0098);Loss of disorder (P = 0.0098);Loss of disorder (P = 0.0098);
MVP		0.32
MPC		0.47
ClinPred		0.65	D
GERP RS		-2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.058
gMVP		0.37
Mutation Taster		=94/6	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: rs371823661; hg19: chr2-74717230;