Variant chr3-100576960-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_018004.3(TMEM45A):c.770C>T(p.Ser257Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000682 in 1,613,506 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 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

TMEM45A
NM_018004.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.62

Variant links:

Genes affected

TMEM45A (HGNC:25480): (transmembrane protein 45A) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM45A links:

TMEM45A (HGNC:):

TMEM45A 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=0.16646668).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM45A	NM_018004.3 linkuse as main transcript	c.770C>T	p.Ser257Leu	missense_variant	6/6	ENST00000323523.8	NP_060474.1	Q9NWC5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TMEM45A	ENST00000323523.8 linkuse as main transcript	c.770C>T	p.Ser257Leu	missense_variant	6/6	1	NM_018004.3	ENSP00000319009.4	Q9NWC5
TMEM45A	ENST00000489060.1 linkuse as main transcript	n.4131C>T		non_coding_transcript_exon_variant	3/3	1
TMEM45A	ENST00000403410.5 linkuse as main transcript	c.818C>T	p.Ser273Leu	missense_variant	8/8	5		ENSP00000385089.1	J3KQ06
TMEM45A	ENST00000488904.1 linkuse as main transcript	n.326C>T		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152172

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1461334

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

726994

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000809

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152172

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74340

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:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000660

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.0000545

EpiControl

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

Apr 23, 2024

The c.770C>T (p.S257L) alteration is located in exon 6 (coding exon 5) of the TMEM45A gene. This alteration results from a C to T substitution at nucleotide position 770, causing the serine (S) at amino acid position 257 to be replaced by a leucine (L). 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

0.12

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.019

T;.

Eigen

Uncertain

0.22

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Benign

0.51

LIST_S2

Uncertain

0.89

D;D

M_CAP

Benign

0.0063

MetaRNN

Benign

0.17

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.4

M;.

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.7

N;N

REVEL

Benign

0.088

Sift

Benign

0.69

T;T

Sift4G

Benign

0.48

T;T

Polyphen

0.78

P;.

Vest4

0.10

MutPred

0.43

Loss of disorder (P = 0.0376);.;

MVP

0.32

MPC

0.65

ClinPred

0.94

GERP RS

5.9

Varity_R

0.081

gMVP

0.17

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