Variant 16-75464597-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_145254.3(TMEM170A):c.4G>A(p.Glu2Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000126 in 1,584,206 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

TMEM170A
NM_145254.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.59

Variant links:

Genes affected

TMEM170A (HGNC:29577): (transmembrane protein 170A) Involved in endoplasmic reticulum tubular network organization; nuclear envelope organization; and nuclear pore complex assembly. Located in endoplasmic reticulum membrane and nuclear envelope. [provided by Alliance of Genome Resources, Apr 2022]

TMEM170A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23208514).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
TMEM170A	NM_145254.3 linkuse as main transcript	c.4G>A	p.Glu2Lys	missense_variant	1/3	ENST00000561878.2
TMEM170A	NM_001304996.2 linkuse as main transcript	c.4G>A	p.Glu2Lys	missense_variant	1/3
TMEM170A	NM_001304998.1 linkuse as main transcript	c.-3+75G>A		intron_variant
TMEM170A	XM_017022941.2 linkuse as main transcript	c.-3+75G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM170A	ENST00000561878.2 linkuse as main transcript	c.4G>A	p.Glu2Lys	missense_variant	1/3	1	NM_145254.3	P1	Q8WVE7-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152266

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000133

AC:

AN:

1431940

Hom.:

Cov.:

AF XY:

0.00000983

AC XY:

AN XY:

712220

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000120

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000155

Gnomad4 OTH exome

AF:

0.0000169

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152266

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 17, 2024

The c.4G>A (p.E2K) alteration is located in exon 1 (coding exon 1) of the TMEM170A gene. This alteration results from a G to A substitution at nucleotide position 4, causing the glutamic acid (E) at amino acid position 2 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.043

BayesDel_noAF

Benign

-0.30

CADD

Uncertain

DANN

Uncertain

1.0

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.41

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.67

T;.;T;T

M_CAP

Benign

0.053

MetaRNN

Benign

0.23

T;T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

D;D;N;N;N

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

0.20

N;N;N;N

Sift

Benign

0.040

D;T;T;T

Polyphen

0.16, 0.24

.;B;B;.

Vest4

0.47, 0.48, 0.52

MutPred

0.23

Gain of ubiquitination at E2 (P = 0.0069);Gain of ubiquitination at E2 (P = 0.0069);Gain of ubiquitination at E2 (P = 0.0069);Gain of ubiquitination at E2 (P = 0.0069);

MVP

0.20

MPC

0.47

ClinPred

0.71

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.19

gMVP

0.79

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over