2-112055658-G-C

Position:

• chr2-112055658-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032824.3(TMEM87B):​c.67G>C​(p.Ala23Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: TMEM87B NM_032824.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0860

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 (HGNC:):

ACMG classification

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=0.12133184).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM87B	NM_032824.3	c.67G>C	p.Ala23Pro	missense_variant	1/19	ENST00000283206.9	NP_116213.1
TMEM87B	NM_001329914.2	c.67G>C	p.Ala23Pro	missense_variant	1/19		NP_001316843.1
TMEM87B	XM_005263827.3	c.67G>C	p.Ala23Pro	missense_variant	1/19		XP_005263884.1
TMEM87B	XR_923049.2	n.390G>C		non_coding_transcript_exon_variant	1/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM87B	ENST00000283206.9	c.67G>C	p.Ala23Pro	missense_variant	1/19	2	NM_032824.3	ENSP00000283206.4
TMEM87B	ENST00000650799.2	c.67G>C	p.Ala23Pro	missense_variant	1/19			ENSP00000498298.2
TMEM87B	ENST00000452614.6	c.67G>C	p.Ala23Pro	missense_variant	1/18	1		ENSP00000393998.2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 34

Bravo AF: 0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 23, 2024

The c.67G>C (p.A23P) alteration is located in exon 1 (coding exon 1) of the TMEM87B gene. This alteration results from a G to C substitution at nucleotide position 67, causing the alanine (A) at amino acid position 23 to be replaced by a proline (P). 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	0.066
BayesDel_addAF	Benign	-0.072	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.017	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0036	N
LIST_S2	Benign	0.58	T
M_CAP	Pathogenic	0.37	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.1	M
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.020
Sift	Benign	0.13	T
Sift4G	Benign	0.21	T
Polyphen		0.0	B
Vest4		0.097
MutPred		0.39		Gain of glycosylation at A23 (P = 0.0053);
MVP		0.17
MPC		0.27
ClinPred		0.28	T
GERP RS		-6.0
Varity_R		0.46
gMVP		0.44

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

Other links and lift over

dbSNP: rs1026928944; hg19: chr2-112813235;