6-52686033-T-G

Position:

• chr6-52686033-T-G

Variant summary

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

The NM_014051.4(TMEM14A):​c.284T>G​(p.Val95Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TMEM14A NM_014051.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.19

Genes affected

TMEM14A (HGNC:21076): (transmembrane protein 14A) Involved in negative regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway. Located in endoplasmic reticulum membrane and mitochondrial membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM14A	NM_014051.4	c.284T>G	p.Val95Gly	missense_variant	5/5	ENST00000211314.5	NP_054770.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM14A	ENST00000211314.5	c.284T>G	p.Val95Gly	missense_variant	5/5	1	NM_014051.4	ENSP00000211314	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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

Aug 02, 2023

The c.284T>G (p.V95G) alteration is located in exon 5 (coding exon 4) of the TMEM14A gene. This alteration results from a T to G substitution at nucleotide position 284, causing the valine (V) at amino acid position 95 to be replaced by a glycine (G). 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	0.13
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.015	T
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Benign	0.45	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.55	D
MetaSVM	Benign	-0.92	T
MutationTaster	Benign	1.0	D
PrimateAI	Benign	0.35	T
PROVEAN	Benign	0.76	N
REVEL	Uncertain	0.29
Sift	Benign	0.19	T
Sift4G	Benign	0.34	T
Polyphen		0.79	P
Vest4		0.45
MutPred		0.78		Loss of stability (P = 2e-04);
MVP		0.54
MPC		0.44
ClinPred		0.96	D
GERP RS		6.0
Varity_R		0.12
gMVP		0.63

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: chr6-52550831;