2-112081349-G-A

Position:

chr2-112081349-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The ENST00000452614.6(TMEM87B):c.618G>A(p.Met206Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000624 in 1,601,614 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

TMEM87B
ENST00000452614.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 10.0

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.856

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM87B	NM_032824.3 linkuse as main transcript	c.669G>A	p.Met223Ile	missense_variant	8/19	ENST00000283206.9	NP_116213.1	Q96K49-1
TMEM87B	NM_001329914.2 linkuse as main transcript	c.669G>A	p.Met223Ile	missense_variant	8/19		NP_001316843.1	A0A494BZZ8
TMEM87B	XM_005263827.3 linkuse as main transcript	c.666G>A	p.Met222Ile	missense_variant	8/19		XP_005263884.1	Q96K49-2
TMEM87B	XR_923049.2 linkuse as main transcript	n.992G>A		non_coding_transcript_exon_variant	8/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TMEM87B	ENST00000283206.9 linkuse as main transcript	c.669G>A	p.Met223Ile	missense_variant	8/19	2	NM_032824.3	ENSP00000283206.4	Q96K49-1
TMEM87B	ENST00000650799.2 linkuse as main transcript	c.669G>A	p.Met223Ile	missense_variant	8/19			ENSP00000498298.2	A0A494BZZ8
TMEM87B	ENST00000452614.6 linkuse as main transcript	c.618G>A	p.Met206Ile	missense_variant	7/18	1		ENSP00000393998.2	H7C0B3
TMEM87B	ENST00000452029.1 linkuse as main transcript	n.399G>A		non_coding_transcript_exon_variant	6/6	1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152182

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:

0.00000552

AC:

AN:

1449432

Hom.:

Cov.:

AF XY:

0.00000971

AC XY:

AN XY:

720670

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000118

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000120

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000361

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152182

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74344

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

Bravo

AF:

0.00000756

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

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

Apr 19, 2023

The c.669G>A (p.M223I) alteration is located in exon 8 (coding exon 8) of the TMEM87B gene. This alteration results from a G to A substitution at nucleotide position 669, causing the methionine (M) at amino acid position 223 to be replaced by an isoleucine (I). 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

Pathogenic

0.88

BayesDel_addAF

Pathogenic

0.47

BayesDel_noAF

Pathogenic

0.44

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.33

Eigen

Uncertain

0.63

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.029

MetaRNN

Pathogenic

0.86

MetaSVM

Uncertain

-0.26

MutationAssessor

Pathogenic

3.0

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.71

PROVEAN

Uncertain

-3.9

REVEL

Uncertain

0.63

Sift

Uncertain

0.0010

Sift4G

Pathogenic

0.0

Polyphen

0.98

Vest4

0.91

MutPred

0.68

Loss of catalytic residue at M223 (P = 0.0079);

MVP

0.38

MPC

0.60

ClinPred

0.99

GERP RS

5.6

Varity_R

0.93

gMVP

0.94

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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