1-15744272-C-G

Variant names:

• chr1-15744272-C-G
• rs148343257
• NM_001013641.3:c.449C>G

Variant summary

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

The NM_001013641.3(TMEM82):​c.449C>G​(p.Thr150Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000213 in 1,409,650 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T150M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: TMEM82 NM_001013641.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.92

Genes affected

TMEM82 (HGNC:32350): (transmembrane protein 82) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC25A34-AS1 (HGNC:53623): (SLC25A34 and TMEM82 antisense RNA 1)

ACMG classification

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

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM82	NM_001013641.3	c.449C>G	p.Thr150Arg	missense_variant	Exon 4 of 6	ENST00000375782.2	NP_001013663.1
SLC25A34-AS1	NR_149050.1	n.462-4050G>C		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM82	ENST00000375782.2	c.449C>G	p.Thr150Arg	missense_variant	Exon 4 of 6	1	NM_001013641.3	ENSP00000364938.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000213 AC: 3 AN: 1409650 Hom.: 0 Cov.: 31 AF XY: 0.00000430 AC XY: 3 AN XY: 698020

African (AFR) AF: 0.00 AC: 0 AN: 32524

American (AMR) AF: 0.00 AC: 0 AN: 39064

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25408

East Asian (EAS) AF: 0.00 AC: 0 AN: 37508

South Asian (SAS) AF: 0.00 AC: 0 AN: 81150

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39942

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4988

European-Non Finnish (NFE) AF: 0.00000275 AC: 3 AN: 1090472

Other (OTH) AF: 0.00 AC: 0 AN: 58594

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Benign	-0.015	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.097	T
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.029	D
MetaRNN	Uncertain	0.62	D
MetaSVM	Benign	-0.53	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		2.9
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-4.0	D
REVEL	Benign	0.19
Sift	Benign	0.053	T
Sift4G	Uncertain	0.055	T
Polyphen		1.0	D
Vest4		0.60
MutPred		0.39		Gain of methylation at T150 (P = 0.0349);
MVP		0.44
MPC		0.44
ClinPred		0.99	D
GERP RS		5.3
Varity_R		0.57
gMVP		0.61
Mutation Taster		=81/19	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Other links and lift over

dbSNP: rs148343257; hg19: chr1-16070767;