2-27033086-C-G

Position:

• chr2-27033086-C-G

Variant summary

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

The ENST00000238788.14(TMEM214):​c.71C>G​(p.Ala24Gly) 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: TMEM214 ENST00000238788.14 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.37

Genes affected

TMEM214 (HGNC:25983): (transmembrane protein 214) Predicted to be involved in apoptotic process. Located in several cellular components, including Golgi apparatus; cytoplasmic microtubule; and endoplasmic reticulum. [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=0.21885741).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM214	NM_017727.5	c.71C>G	p.Ala24Gly	missense_variant	1/17	ENST00000238788.14	NP_060197.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM214	ENST00000238788.14	c.71C>G	p.Ala24Gly	missense_variant	1/17	1	NM_017727.5	ENSP00000238788	P1

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 16, 2021

The c.71C>G (p.A24G) alteration is located in exon 1 (coding exon 1) of the TMEM214 gene. This alteration results from a C to G substitution at nucleotide position 71, causing the alanine (A) at amino acid position 24 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	0.049
BayesDel_addAF	Benign	-0.086	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	9.0
DANN	Benign	0.50
DEOGEN2	Benign	0.0054	T;.
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.30	T;T
M_CAP	Pathogenic	0.81	D
MetaRNN	Benign	0.22	T;T
MetaSVM	Benign	-0.75	T
MutationAssessor	Benign	1.4	L;L
MutationTaster	Benign	1.0	N;N
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.13	N;N
REVEL	Benign	0.13
Sift	Benign	0.68	T;T
Sift4G	Benign	0.68	T;T
Polyphen		0.0	B;B
Vest4		0.15
MutPred		0.19		Gain of catalytic residue at P20 (P = 0.0793);Gain of catalytic residue at P20 (P = 0.0793);
MVP		0.38
MPC		0.26
ClinPred		0.088	T
GERP RS		3.2
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		3.6
Varity_R		0.042
gMVP		0.19

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: chr2-27255954;