2-112066951-C-T

Position:

• chr2-112066951-C-T

Variant summary

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

The ENST00000452614.6(TMEM87B):​c.334C>T​(p.His112Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 1,452,166 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 Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: TMEM87B ENST00000452614.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.25

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=0.07844448).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM87B	NM_032824.3	c.334C>T	p.His112Tyr	missense_variant	4/19	ENST00000283206.9	NP_116213.1
TMEM87B	NM_001329914.2	c.334C>T	p.His112Tyr	missense_variant	4/19		NP_001316843.1
TMEM87B	XM_005263827.3	c.334C>T	p.His112Tyr	missense_variant	4/19		XP_005263884.1
TMEM87B	XR_923049.2	n.657C>T		non_coding_transcript_exon_variant	4/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM87B	ENST00000283206.9	c.334C>T	p.His112Tyr	missense_variant	4/19	2	NM_032824.3	ENSP00000283206.4
TMEM87B	ENST00000650799.2	c.334C>T	p.His112Tyr	missense_variant	4/19			ENSP00000498298.2
TMEM87B	ENST00000452614.6	c.334C>T	p.His112Tyr	missense_variant	4/18	1		ENSP00000393998.2
TMEM87B	ENST00000452029.1	n.206C>T		non_coding_transcript_exon_variant	4/6	1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000275 AC: 4 AN: 1452166 Hom.: 0 Cov.: 30 AF XY: 0.00000277 AC XY: 2 AN XY: 722042

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: 0.00000271

Gnomad4 OTH exome AF: 0.0000167

GnomAD4 genome Cov.: 33

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 18, 2023

The c.334C>T (p.H112Y) alteration is located in exon 4 (coding exon 4) of the TMEM87B gene. This alteration results from a C to T substitution at nucleotide position 334, causing the histidine (H) at amino acid position 112 to be replaced by a tyrosine (Y). 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	0.083
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	18
DANN	Benign	0.80
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.060
Eigen_PC	Benign	-0.12
FATHMM_MKL	Benign	0.34	N
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.078	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.5	M
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.12
Sift	Benign	0.22	T
Sift4G	Benign	0.96	T
Polyphen		0.0040	B
Vest4		0.17
MutPred		0.42		Loss of disorder (P = 0.0435);
MVP		0.099
MPC		0.18
ClinPred		0.69	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.10
gMVP		0.51

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-112824528;