1-15219378-A-G

Variant names:

• chr1-15219378-A-G
• NM_001136218.2:c.397A>G

Variant summary

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

The NM_001136218.2(TMEM51):​c.397A>G​(p.Ser133Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,456,922 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: TMEM51 NM_001136218.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.89
• Publications: 0 publications found

Genes affected

TMEM51 (HGNC:25488): (transmembrane protein 51) 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_001136218.2. 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
	TMEM51	NM_001136218.2	MANE Select	c.397A>G	p.Ser133Gly	missense	Exon 4 of 4	NP_001129690.1	Q9NW97
	TMEM51	NM_001136216.2		c.397A>G	p.Ser133Gly	missense	Exon 4 of 4	NP_001129688.1	Q9NW97
	TMEM51	NM_001136217.2		c.397A>G	p.Ser133Gly	missense	Exon 3 of 3	NP_001129689.1	Q9NW97

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM51	ENST00000376008.3	TSL:2 MANE Select	c.397A>G	p.Ser133Gly	missense	Exon 4 of 4	ENSP00000365176.1	Q9NW97
	TMEM51	ENST00000400796.7	TSL:1	c.397A>G	p.Ser133Gly	missense	Exon 3 of 3	ENSP00000383600.2	Q9NW97
	TMEM51	ENST00000434578.6	TSL:1	c.393A>G	p.Pro131Pro	synonymous	Exon 4 of 4	ENSP00000409665.2	Q9BSA0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1456922 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 723810

African (AFR) AF: 0.00 AC: 0 AN: 33348

American (AMR) AF: 0.00 AC: 0 AN: 44376

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25994

East Asian (EAS) AF: 0.00 AC: 0 AN: 39572

South Asian (SAS) AF: 0.00 AC: 0 AN: 85934

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53346

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

European-Non Finnish (NFE) AF: 9.02e-7 AC: 1 AN: 1108478

Other (OTH) AF: 0.00 AC: 0 AN: 60122

GnomAD4 genome Cov.: 32

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	Uncertain	0.47
BayesDel_addAF	Benign	-0.0069	T
BayesDel_noAF	Benign	-0.25
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	T
Eigen	Pathogenic	0.70
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.027	D
MetaRNN	Uncertain	0.64	D
MetaSVM	Benign	-0.61	T
MutationAssessor	Uncertain	2.9	M
PhyloP100		5.9
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.21
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0050	D
Polyphen		1.0	D
Vest4		0.79
MutPred		0.18		Gain of sheet (P = 0.0125)
MVP		0.22
MPC		0.69
ClinPred		0.98	D
GERP RS		5.6
Varity_R		0.65
gMVP		0.48
Mutation Taster		=76/24	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

hg19: chr1-15545874;