chr2-112055697-A-G

Position:

chr2-112055697-A-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The ENST00000452614.6(TMEM87B):c.106A>G(p.Thr36Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000128 in 1,404,274 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

TMEM87B
ENST00000452614.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.551

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 Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.024461687).

BP6

Variant 2-112055697-A-G is Benign according to our data. Variant chr2-112055697-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2260166.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM87B	NM_032824.3 linkuse as main transcript	c.106A>G	p.Thr36Ala	missense_variant	1/19	ENST00000283206.9	NP_116213.1	Q96K49-1
TMEM87B	NM_001329914.2 linkuse as main transcript	c.106A>G	p.Thr36Ala	missense_variant	1/19		NP_001316843.1	A0A494BZZ8
TMEM87B	XM_005263827.3 linkuse as main transcript	c.106A>G	p.Thr36Ala	missense_variant	1/19		XP_005263884.1	Q96K49-2
TMEM87B	XR_923049.2 linkuse as main transcript	n.429A>G		non_coding_transcript_exon_variant	1/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TMEM87B	ENST00000283206.9 linkuse as main transcript	c.106A>G	p.Thr36Ala	missense_variant	1/19	2	NM_032824.3	ENSP00000283206.4	Q96K49-1
TMEM87B	ENST00000650799.2 linkuse as main transcript	c.106A>G	p.Thr36Ala	missense_variant	1/19			ENSP00000498298.2	A0A494BZZ8
TMEM87B	ENST00000452614.6 linkuse as main transcript	c.106A>G	p.Thr36Ala	missense_variant	1/18	1		ENSP00000393998.2	H7C0B3
TMEM87B	ENST00000452029.1 linkuse as main transcript	n.-23A>G		upstream_gene_variant		1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000279

AC:

AN:

178910

Hom.:

AF XY:

0.0000296

AC XY:

AN XY:

101382

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000411

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:

0.0000369

Gnomad OTH exome

AF:

0.000247

GnomAD4 exome

AF:

0.0000128

AC:

AN:

1404274

Hom.:

Cov.:

AF XY:

0.0000129

AC XY:

AN XY:

697418

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:

0.0000156

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000335

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 09, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.052

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.70

DEOGEN2

Benign

0.0070

Eigen

Benign

-0.89

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.0032

LIST_S2

Benign

0.13

M_CAP

Benign

0.054

MetaRNN

Benign

0.024

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.9

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.79

PROVEAN

Benign

0.67

REVEL

Benign

0.024

Sift

Benign

1.0

Sift4G

Benign

0.96

Polyphen

0.0

Vest4

0.023

MutPred

0.42

Loss of catalytic residue at T36 (P = 0.1468);

MVP

0.030

MPC

0.12

ClinPred

0.021

GERP RS

0.62

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.044

gMVP

0.18

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