4-4246268-G-A

Position:

• chr4-4246268-G-A

Variant summary

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

The NM_001297551.2(TMEM128):​c.173C>T​(p.Ala58Val) variant causes a missense change involving the alteration of a 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: TMEM128 NM_001297551.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.09

Genes affected

TMEM128 (HGNC:28201): (transmembrane protein 128) Predicted to be integral component of 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	UniProt
TMEM128	NM_001297551.2	c.173C>T	p.Ala58Val	missense_variant	2/5	ENST00000382753.5
TMEM128	NM_001297552.2	c.173C>T	p.Ala58Val	missense_variant	2/5
TMEM128	NM_032927.4	c.101C>T	p.Ala34Val	missense_variant	2/5
TMEM128	XM_005248034.4	c.173C>T	p.Ala58Val	missense_variant	2/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM128	ENST00000382753.5	c.173C>T	p.Ala58Val	missense_variant	2/5	1	NM_001297551.2	P1
TMEM128	ENST00000254742.6	c.101C>T	p.Ala34Val	missense_variant	2/5	1

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

Mar 29, 2022

The c.101C>T (p.A34V) alteration is located in exon 2 (coding exon 2) of the TMEM128 gene. This alteration results from a C to T substitution at nucleotide position 101, causing the alanine (A) at amino acid position 34 to be replaced by a valine (V). 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	0.20
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.040
CADD	Pathogenic	26
DANN	Uncertain	1.0
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.93	D;D
M_CAP	Benign	0.057	D
MetaRNN	Uncertain	0.62	D;D
MetaSVM	Uncertain	0.17	D
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-2.3	N;N
REVEL	Pathogenic	0.67
Sift	Benign	0.12	T;T
Sift4G	Uncertain	0.0080	D;D
Polyphen		0.90	P;P
Vest4		0.63
MutPred		0.61		.;Gain of sheet (P = 0.0221);
MVP		0.59
MPC		0.36
ClinPred		0.96	D
GERP RS		5.8
Varity_R		0.24
gMVP		0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr4-4247995;