1-43272819-C-G

Variant names:

• chr1-43272819-C-G
• rs779719920
• NM_144626.3:c.97C>G

Variant summary

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

The NM_144626.3(TMEM125):​c.97C>G​(p.Arg33Gly) 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R33C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TMEM125 NM_144626.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.44
• Publications: 0 publications found

Genes affected

TMEM125 (HGNC:28275): (transmembrane protein 125) 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_144626.3. 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
	TMEM125	NM_144626.3	MANE Select	c.97C>G	p.Arg33Gly	missense	Exon 4 of 4	NP_653227.1	Q96AQ2
	TMEM125	NM_001320244.2		c.97C>G	p.Arg33Gly	missense	Exon 4 of 4	NP_001307173.1	Q96AQ2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM125	ENST00000439858.6	TSL:2 MANE Select	c.97C>G	p.Arg33Gly	missense	Exon 4 of 4	ENSP00000429775.1	Q96AQ2
	TMEM125	ENST00000432792.6	TSL:1	c.97C>G	p.Arg33Gly	missense	Exon 4 of 4	ENSP00000429275.1	Q96AQ2
	TMEM125	ENST00000908432.1		c.97C>G	p.Arg33Gly	missense	Exon 3 of 3	ENSP00000578491.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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	Benign	0.25
BayesDel_addAF	Benign	-0.054	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.069	T
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.70	T
M_CAP	Uncertain	0.097	D
MetaRNN	Uncertain	0.52	D
MetaSVM	Benign	-0.58	T
MutationAssessor	Benign	1.6	L
PhyloP100		1.4
PrimateAI	Uncertain	0.62	T
PROVEAN	Pathogenic	-4.7	D
REVEL	Benign	0.14
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.030	D
Polyphen		0.99	D
Vest4		0.48
MutPred		0.38		Loss of MoRF binding (P = 0.0301)
MVP		0.44
MPC		0.66
ClinPred		0.98	D
GERP RS		4.9
Varity_R		0.36
gMVP		0.50
Mutation Taster		=71/29	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: rs779719920; hg19: chr1-43738490;