Variant 15-42273289-G-A 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_015497.5(TMEM87A):c.110C>T(p.Ala37Val) 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 1,461,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

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: 3.09

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:

TMEM87A (HGNC:):

TMEM87A links:

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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=0.10792661).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM87A	NM_015497.5 linkuse as main transcript	c.110C>T	p.Ala37Val	missense_variant	1/20	ENST00000389834.9	NP_056312.2	Q8NBN3-1
GANC	NM_198141.3 linkuse as main transcript	c.-1193G>A		5_prime_UTR_variant	1/24	ENST00000318010.13	NP_937784.2	Q8TET4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TMEM87A	ENST00000389834.9 linkuse as main transcript	c.110C>T	p.Ala37Val	missense_variant	1/20	2	NM_015497.5	ENSP00000374484.4	Q8NBN3-1
TMEM87A	ENST00000566014.2 linkuse as main transcript	c.110C>T	p.Ala37Val	missense_variant	1/20	5		ENSP00000457308.2	H3BTS6
TMEM87A	ENST00000704760.1 linkuse as main transcript	c.110C>T	p.Ala37Val	missense_variant	1/20			ENSP00000516026.1	A0A994J4W5
TMEM87A	ENST00000704761.1 linkuse as main transcript	c.110C>T	p.Ala37Val	missense_variant	1/20			ENSP00000516027.1	A0A994J7M5
GANC	ENST00000318010 linkuse as main transcript	c.-1193G>A		5_prime_UTR_variant	1/24	1	NM_198141.3	ENSP00000326227.8	Q8TET4
TMEM87A	ENST00000448392.6 linkuse as main transcript	n.110C>T		non_coding_transcript_exon_variant	1/19	1		ENSP00000405379.2	H3BRG0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461862

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727236

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:

8.99e-7

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

Oct 09, 2024

The c.110C>T (p.A37V) alteration is located in exon 1 (coding exon 1) of the TMEM87A gene. This alteration results from a C to T substitution at nucleotide position 110, causing the alanine (A) at amino acid position 37 to be replaced by a valine (V). 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

0.28

BayesDel_addAF

Uncertain

0.028

BayesDel_noAF

Benign

-0.20

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.024

T;.

Eigen

Benign

0.15

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Benign

0.31

LIST_S2

Benign

0.83

T;D

M_CAP

Benign

0.015

MetaRNN

Benign

0.11

T;T

MetaSVM

Benign

-0.58

MutationAssessor

Benign

1.3

L;L

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.66

N;N

REVEL

Benign

0.075

Sift

Benign

0.77

T;D

Sift4G

Benign

0.27

T;D

Polyphen

0.010

B;D

Vest4

0.36

MutPred

0.39

Gain of sheet (P = 0.039);Gain of sheet (P = 0.039);

MVP

0.082

MPC

0.29

ClinPred

0.64

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.11

gMVP

0.40

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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