rs140012562

Variant names:

• chr2-74490427-G-A
• rs140012562
• NM_022492.6:c.416G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-74490427-G-A
• chr2-74490427-G-T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_022492.6(TTC31):​c.416G>A​(p.Ser139Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0056 in 1,613,642 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 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. S139I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0050 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0057 (28 hom.)
• Consequence: TTC31 NM_022492.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.539
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0046494007).
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC31	NM_022492.6	c.416G>A	p.Ser139Asn	missense_variant	Exon 4 of 13	ENST00000233623.11	NP_071937.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTC31	ENST00000233623.11	c.416G>A	p.Ser139Asn	missense_variant	Exon 4 of 13	1	NM_022492.6	ENSP00000233623.6

Frequencies

GnomAD3 genomes AF: 0.00504 AC: 766 AN: 152108 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.00111

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00197

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.0236

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00626

Gnomad OTH AF: 0.00431

GnomAD2 exomes AF: 0.00549 AC: 1360 AN: 247872 AF XY: 0.00567

Gnomad AFR exome AF: 0.000846

Gnomad AMR exome AF: 0.00148

Gnomad ASJ exome AF: 0.0000997

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0189

Gnomad NFE exome AF: 0.00729

Gnomad OTH exome AF: 0.00400

GnomAD4 exome AF: 0.00566 AC: 8266 AN: 1461416 Hom.: 28 Cov.: 33 AF XY: 0.00557 AC XY: 4049 AN XY: 726940

African (AFR) AF: 0.000896 AC: 30 AN: 33468

American (AMR) AF: 0.00125 AC: 56 AN: 44640

Ashkenazi Jewish (ASJ) AF: 0.000153 AC: 4 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00156 AC: 134 AN: 86152

European-Finnish (FIN) AF: 0.0188 AC: 1006 AN: 53388

Middle Eastern (MID) AF: 0.00156 AC: 9 AN: 5768

European-Non Finnish (NFE) AF: 0.00608 AC: 6758 AN: 1111802

Other (OTH) AF: 0.00445 AC: 269 AN: 60384

GnomAD4 genome AF: 0.00503 AC: 766 AN: 152226 Hom.: 5 Cov.: 32 AF XY: 0.00580 AC XY: 432 AN XY: 74436

African (AFR) AF: 0.00111 AC: 46 AN: 41540

American (AMR) AF: 0.00196 AC: 30 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000829 AC: 4 AN: 4824

European-Finnish (FIN) AF: 0.0236 AC: 250 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00626 AC: 426 AN: 68006

Other (OTH) AF: 0.00427 AC: 9 AN: 2108

Alfa AF: 0.00587 Hom.: 9

Bravo AF: 0.00335

TwinsUK AF: 0.00351 AC: 13

ALSPAC AF: 0.00649 AC: 25

ESP6500AA AF: 0.00184 AC: 7

ESP6500EA AF: 0.00703 AC: 58

ExAC AF: 0.00588 AC: 711

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00654

EpiControl AF: 0.00594

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	15
DANN	Benign	0.95
DEOGEN2	Benign	0.0025	.;.;T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.60	T;T;T
MetaRNN	Benign	0.0046	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N;.;N
PhyloP100		0.54
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-2.0	.;N;N
REVEL	Benign	0.050
Sift	Benign	0.22	.;T;T
Sift4G	Benign	0.37	T;T;T
Polyphen		0.0040	.;.;B
Vest4		0.075
MVP		0.60
MPC		0.081
ClinPred		0.012	T
GERP RS		1.5
Varity_R		0.028
gMVP		0.057
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs140012562; hg19: chr2-74717554;