Variant 16-75464510-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_145254.3(TMEM170A):c.91G>A(p.Gly31Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000543 in 1,585,044 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000052 ( 0 hom. )

Consequence

TMEM170A
NM_145254.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.88

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:

ENSG00000261717 (HGNC:):

ENSG00000261717 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.033627987).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM170A	NM_145254.3 link	c.91G>A	p.Gly31Arg	missense_variant	1/3	ENST00000561878.2	NP_660297.1	Q8WVE7-1
TMEM170A	NM_001304996.2 link	c.91G>A	p.Gly31Arg	missense_variant	1/3		NP_001291925.1	Q8WVE7-2
TMEM170A	NM_001304998.1 link	c.-3+162G>A		intron_variant			NP_001291927.1	H3BRD7
TMEM170A	XM_017022941.2 link	c.-3+162G>A		intron_variant			XP_016878430.1	H3BS26

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM170A	ENST00000561878.2 link	c.91G>A	p.Gly31Arg	missense_variant	1/3	1	NM_145254.3	ENSP00000454404.1		Q8WVE7-1
ENSG00000261717	ENST00000567194.5 link	c.91G>A	p.Gly31Arg	missense_variant	1/4	2		ENSP00000457654.1		H3BUI4

Frequencies

GnomAD3 genomes

AF:

0.0000788

AC:

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00231

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000845

AC:

AN:

213126

Hom.:

AF XY:

0.0000850

AC XY:

AN XY:

117686

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00181

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000103

Gnomad OTH exome

AF:

0.000200

GnomAD4 exome

AF:

0.0000516

AC:

AN:

1432730

Hom.:

Cov.:

AF XY:

0.0000533

AC XY:

AN XY:

712436

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00218

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000909

Gnomad4 OTH exome

AF:

0.000152

GnomAD4 genome

AF:

0.0000788

AC:

AN:

152314

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.0000240

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00231

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000248

Hom.:

Bravo

AF:

0.0000642

ExAC

AF:

0.0000745

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Oct 26, 2021

The c.91G>A (p.G31R) 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 91, causing the glycine (G) at amino acid position 31 to be replaced by an arginine (R). 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

0.16

BayesDel_addAF

Uncertain

0.077

BayesDel_noAF

Benign

-0.13

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.014

.;.;.;T;.

Eigen

Benign

-0.041

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.85

D;T;.;D;T

M_CAP

Benign

0.072

MetaRNN

Benign

0.034

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

.;.;L;L;.

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-0.45

N;N;N;N;N

REVEL

Benign

0.10

Sift

Uncertain

0.0070

D;D;T;T;T

Sift4G

Benign

0.59

.;.;T;T;T

Polyphen

0.76, 0.65

.;.;P;P;.

Vest4

0.77, 0.67, 0.83

MutPred

0.47

Gain of MoRF binding (P = 0.0416);.;Gain of MoRF binding (P = 0.0416);Gain of MoRF binding (P = 0.0416);Gain of MoRF binding (P = 0.0416);

MVP

0.69

MPC

0.19

ClinPred

0.14

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.12

gMVP

0.84

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