17-50279293-C-A

Variant names:

• chr17-50279293-C-A
• NM_153229.3:c.465C>A

Variant summary

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

The NM_153229.3(TMEM92):​c.465C>A​(p.Asp155Glu) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TMEM92 NM_153229.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.933

Genes affected

TMEM92 (HGNC:26579): (transmembrane protein 92) Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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=0.18743932).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM92	NM_153229.3	c.465C>A	p.Asp155Glu	missense_variant	Exon 5 of 5	ENST00000507382.2	NP_694961.2
TMEM92	NM_001168215.2	c.465C>A	p.Asp155Glu	missense_variant	Exon 6 of 6		NP_001161687.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM92	ENST00000507382.2	c.465C>A	p.Asp155Glu	missense_variant	Exon 5 of 5	1	NM_153229.3	ENSP00000425144.1
TMEM92	ENST00000300433.7	c.465C>A	p.Asp155Glu	missense_variant	Exon 6 of 6	1		ENSP00000300433.3
TMEM92	ENST00000511882.1	n.*177C>A		downstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 01, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.465C>A (p.D155E) alteration is located in exon 6 (coding exon 5) of the TMEM92 gene. This alteration results from a C to A substitution at nucleotide position 465, causing the aspartic acid (D) at amino acid position 155 to be replaced by a glutamic acid (E). 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	0.31
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.056	T;T
Eigen	Benign	0.055
Eigen_PC	Benign	-0.050
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.42	.;T
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.19	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L;L
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.9	N;N
REVEL	Benign	0.051
Sift	Uncertain	0.0080	D;D
Sift4G	Benign	0.47	T;T
Polyphen		0.97	D;D
Vest4		0.25
MutPred		0.20		Gain of sheet (P = 0.1451);Gain of sheet (P = 0.1451);
MVP		0.37
MPC		0.78
ClinPred		0.73	D
GERP RS		3.5
Varity_R		0.066
gMVP		0.12

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: chr17-48356654;