Variant chr3-100568880-A-C 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.647A>C(p.Glu216Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000193 in 1,613,864 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00020 ( 0 hom. )

Consequence

TMEM45A
NM_018004.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.615

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=0.18865511).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM45A	NM_018004.3 linkuse as main transcript	c.647A>C	p.Glu216Ala	missense_variant	5/6	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.647A>C	p.Glu216Ala	missense_variant	5/6	1	NM_018004.3	ENSP00000319009.4	Q9NWC5
TMEM45A	ENST00000403410.5 linkuse as main transcript	c.695A>C	p.Glu232Ala	missense_variant	7/8	5		ENSP00000385089.1	J3KQ06
TMEM45A	ENST00000485260.1 linkuse as main transcript	n.59A>C		non_coding_transcript_exon_variant	1/2	2
TMEM45A	ENST00000489060.1 linkuse as main transcript	n.-44A>C		upstream_gene_variant		1

Frequencies

GnomAD3 genomes

AF:

0.000138

AC:

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.000250

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000995

AC:

AN:

251322

Hom.:

AF XY:

0.0000810

AC XY:

AN XY:

135820

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000220

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000198

AC:

290

AN:

1461658

Hom.:

Cov.:

AF XY:

0.000194

AC XY:

141

AN XY:

727134

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

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:

0.000249

Gnomad4 OTH exome

AF:

0.000132

GnomAD4 genome

AF:

0.000138

AC:

AN:

152206

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000250

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000245

Hom.:

Bravo

AF:

0.000155

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.0000576

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

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

Dec 16, 2022

The c.647A>C (p.E216A) alteration is located in exon 5 (coding exon 4) of the TMEM45A gene. This alteration results from a A to C substitution at nucleotide position 647, causing the glutamic acid (E) at amino acid position 216 to be replaced by an alanine (A). 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

0.15

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Benign

0.75

DEOGEN2

Benign

0.027

T;.

Eigen

Benign

-0.81

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.75

T;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.19

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.40

N;.

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.033

Sift

Benign

0.55

T;T

Sift4G

Benign

0.42

T;T

Polyphen

0.014

B;.

Vest4

0.15

MVP

0.11

MPC

0.30

ClinPred

0.032

GERP RS

3.4

Varity_R

0.046

gMVP

0.28

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