1-32216929-A-C

Position:

• chr1-32216929-A-C

Variant summary

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

The NM_019118.5(TMEM234):​c.347T>G​(p.Val116Gly) 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: TMEM234 NM_019118.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.13

Genes affected

TMEM234 (HGNC:28837): (transmembrane protein 234) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM234 (HGNC:):

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
TMEM234	NM_019118.5	c.347T>G	p.Val116Gly	missense_variant	5/5	ENST00000309777.11	NP_061991.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM234	ENST00000309777.11	c.347T>G	p.Val116Gly	missense_variant	5/5	1	NM_019118.5	ENSP00000309792.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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

Oct 10, 2023

The c.347T>G (p.V116G) alteration is located in exon 5 (coding exon 5) of the TMEM234 gene. This alteration results from a T to G substitution at nucleotide position 347, causing the valine (V) at amino acid position 116 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	0.10
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.089	.;T
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.70	T;T
M_CAP	Benign	0.049	D
MetaRNN	Uncertain	0.52	D;D
MetaSVM	Benign	-0.74	T
MutationAssessor	Benign	1.2	L;L
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-3.1	D;D
REVEL	Uncertain	0.50
Sift	Uncertain	0.0050	D;T
Sift4G	Uncertain	0.015	D;D
Polyphen		0.97	D;.
Vest4		0.45
MutPred		0.50		Loss of stability (P = 9e-04);Loss of stability (P = 9e-04);
MVP		0.42
MPC		0.29
ClinPred		0.87	D
GERP RS		3.9
Varity_R		0.21
gMVP		0.14

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: chr1-32682530;