chr4-4240327-C-T

Variant names:

• chr4-4240327-C-T
• rs1717895843
• NM_001297551.2:c.392G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001297551.2(TMEM128):​c.392G>A​(p.Gly131Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000144 in 1,460,400 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: TMEM128 NM_001297551.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.80
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001297551.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM128	NM_001297551.2	MANE Select	c.392G>A	p.Gly131Glu	missense	Exon 3 of 5	NP_001284480.1	Q5BJH2-1
	TMEM128	NM_001297552.2		c.392G>A	p.Gly131Glu	missense	Exon 3 of 5	NP_001284481.1	Q5BJH2-1
	TMEM128	NM_032927.4		c.320G>A	p.Gly107Glu	missense	Exon 3 of 5	NP_116316.1	Q5BJH2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM128	ENST00000382753.5	TSL:1 MANE Select	c.392G>A	p.Gly131Glu	missense	Exon 3 of 5	ENSP00000372201.4	Q5BJH2-1
	TMEM128	ENST00000254742.6	TSL:1	c.320G>A	p.Gly107Glu	missense	Exon 3 of 5	ENSP00000254742.2	Q5BJH2-2
	TMEM128	ENST00000898375.1		c.515G>A	p.Gly172Glu	missense	Exon 4 of 6	ENSP00000568434.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000144 AC: 21 AN: 1460400 Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8 AN XY: 726478

African (AFR) AF: 0.0000299 AC: 1 AN: 33412

American (AMR) AF: 0.0000226 AC: 1 AN: 44234

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26042

East Asian (EAS) AF: 0.00 AC: 0 AN: 39680

South Asian (SAS) AF: 0.00 AC: 0 AN: 85984

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 0.0000162 AC: 18 AN: 1111570

Other (OTH) AF: 0.0000166 AC: 1 AN: 60324

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.90
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.020	T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.052	D
MetaRNN	Uncertain	0.59	D
MetaSVM	Uncertain	0.44	D
MutationAssessor	Uncertain	2.6	M
PhyloP100		4.8
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-1.6	N
REVEL	Uncertain	0.55
Sift	Benign	0.050	D
Sift4G	Benign	0.31	T
Polyphen		0.96	D
Vest4		0.50
MutPred		0.53		Loss of glycosylation at S126 (P = 0.0328)
MVP		0.71
MPC		0.57
ClinPred		0.95	D
GERP RS		4.5
Varity_R		0.21
gMVP		0.84
Mutation Taster		=72/28	polymorphism

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

Other links and lift over

dbSNP: rs1717895843; hg19: chr4-4242054;