2-112077192-G-C

Position:

chr2-112077192-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032824.3(TMEM87B):c.502G>C(p.Asp168His) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000512 in 1,561,534 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/24 in silico tools predict a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000055 ( 0 hom. )

Consequence

TMEM87B
NM_032824.3 missense, splice_region

Scores

Splicing: ADA: 0.6923

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.29

Variant links:

Genes affected

TMEM87B (HGNC:25913): (transmembrane protein 87B) This gene encodes a protein that may interact with human papillomavirus type 18 E6 oncogene. The protein is also likely to be involved in endosome-to-trans-Golgi network retrograde transport. The gene is expressed in adult and fetal tissues, including brain and heart. This gene is a component of the 2q13 deletion syndrome. Mutations in this gene may be associated with congenital heart defects. [provided by RefSeq, Aug 2016]

TMEM87B links:

TMEM87B (HGNC:):

TMEM87B 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=0.20724258).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM87B	NM_032824.3 linkuse as main transcript	c.502G>C	p.Asp168His	missense_variant, splice_region_variant	6/19	ENST00000283206.9	NP_116213.1	Q96K49-1
TMEM87B	NM_001329914.2 linkuse as main transcript	c.502G>C	p.Asp168His	missense_variant, splice_region_variant	6/19		NP_001316843.1	A0A494BZZ8
TMEM87B	XM_005263827.3 linkuse as main transcript	c.499G>C	p.Asp167His	missense_variant, splice_region_variant	6/19		XP_005263884.1	Q96K49-2
TMEM87B	XR_923049.2 linkuse as main transcript	n.825G>C		splice_region_variant, non_coding_transcript_exon_variant	6/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TMEM87B	ENST00000283206.9 linkuse as main transcript	c.502G>C	p.Asp168His	missense_variant, splice_region_variant	6/19	2	NM_032824.3	ENSP00000283206.4	Q96K49-1
TMEM87B	ENST00000650799.2 linkuse as main transcript	c.502G>C	p.Asp168His	missense_variant, splice_region_variant	6/19			ENSP00000498298.2	A0A494BZZ8
TMEM87B	ENST00000452614.6 linkuse as main transcript	c.451G>C	p.Asp151His	missense_variant, splice_region_variant	5/18	1		ENSP00000393998.2	H7C0B3
TMEM87B	ENST00000452029.1 linkuse as main transcript	n.323-3865G>C		intron_variant		1

Frequencies

GnomAD3 genomes

AF:

0.0000198

AC:

AN:

151814

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:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000131

AC:

AN:

229824

Hom.:

AF XY:

0.00000801

AC XY:

AN XY:

124838

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:

0.0000276

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000546

AC:

AN:

1409720

Hom.:

Cov.:

AF XY:

0.0000513

AC XY:

AN XY:

701646

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:

0.0000701

Gnomad4 OTH exome

AF:

0.0000172

GnomAD4 genome

AF:

0.0000198

AC:

AN:

151814

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74128

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:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.00000824

AC:

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 31, 2023

The c.502G>C (p.D168H) alteration is located in exon 6 (coding exon 6) of the TMEM87B gene. This alteration results from a G to C substitution at nucleotide position 502, causing the aspartic acid (D) at amino acid position 168 to be replaced by a histidine (H). 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

0.26

BayesDel_addAF

Benign

-0.017

BayesDel_noAF

Benign

-0.19

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.010

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.80

M_CAP

Benign

0.024

MetaRNN

Benign

0.21

MetaSVM

Benign

-0.73

MutationAssessor

Uncertain

2.6

PrimateAI

Benign

0.45

PROVEAN

Benign

-1.6

REVEL

Benign

0.097

Sift

Benign

0.37

Sift4G

Benign

0.37

Polyphen

0.093

Vest4

0.39

MVP

0.47

MPC

0.22

ClinPred

0.37

GERP RS

4.8

Varity_R

0.20

gMVP

0.62

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.69

dbscSNV1_RF

Benign

0.48

SpliceAI score (max)

0.37

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.37

Position offset: 0

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