Variant 15-42273302-T-C 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_015497.5(TMEM87A):c.97A>G(p.Thr33Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,858 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TMEM87A
NM_015497.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0210

Variant links:

Genes affected

TMEM87A (HGNC:24522): (transmembrane protein 87A) Involved in retrograde transport, endosome to Golgi. Located in Golgi cisterna membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM87A links:

GANC (HGNC:4139): (glucosidase alpha, neutral C) Glycosyl hydrolase enzymes hydrolyse the glycosidic bond between two or more carbohydrates, or between a carbohydrate and a non-carbohydrate moiety. This gene encodes a member of glycosyl hydrolases family 31. This enzyme hydrolyses terminal, non-reducing 1,4-linked alpha-D-glucose residues and releases alpha-D-glucose. This is a key enzyme in glycogen metabolism and its gene localizes to a chromosomal region (15q15) that is associated with susceptibility to diabetes. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Aug 2014]

GANC 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=0.032305777).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM87A	NM_015497.5 linkuse as main transcript	c.97A>G	p.Thr33Ala	missense_variant	1/20	ENST00000389834.9	NP_056312.2
GANC	NM_198141.3 linkuse as main transcript	c.-1180T>C		5_prime_UTR_variant	1/24	ENST00000318010.13	NP_937784.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM87A	ENST00000389834.9 linkuse as main transcript	c.97A>G	p.Thr33Ala	missense_variant	1/20	2	NM_015497.5	ENSP00000374484	P4	Q8NBN3-1
GANC	ENST00000318010.13 linkuse as main transcript	c.-1180T>C		5_prime_UTR_variant	1/24	1	NM_198141.3	ENSP00000326227	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461858

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727234

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

May 07, 2024

The c.97A>G (p.T33A) alteration is located in exon 1 (coding exon 1) of the TMEM87A gene. This alteration results from a A to G substitution at nucleotide position 97, causing the threonine (T) at amino acid position 33 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

0.056

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.62

CADD

Benign

8.4

DANN

Benign

0.93

DEOGEN2

Benign

0.016

T;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.88

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.20

T;T

M_CAP

Benign

0.0024

MetaRNN

Benign

0.032

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;N

MutationTaster

Benign

1.0

D;N;N

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.090

N;N

REVEL

Benign

0.028

Sift

Benign

0.97

T;T

Sift4G

Benign

0.67

T;T

Polyphen

0.0

B;B

Vest4

0.043

MutPred

0.28

Gain of helix (P = 0.005);Gain of helix (P = 0.005);

MVP

0.043

MPC

0.26

ClinPred

0.077

GERP RS

2.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.036

gMVP

0.24

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over