chr1-15744515-C-T

Variant names:

• chr1-15744515-C-T
• rs59905655
• NM_001013641.3:c.692C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001013641.3(TMEM82):​c.692C>T​(p.Ser231Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00101 in 1,612,576 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0051 (5 hom., cov: 33)
  • Exomes 𝑓: 0.00058 (12 hom.)
• Consequence: TMEM82 NM_001013641.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.79
• Publications: 9 publications found

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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008479118).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00511 (778/152368) while in subpopulation AFR AF = 0.0175 (727/41590). AF 95% confidence interval is 0.0164. There are 5 homozygotes in GnomAd4. There are 386 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001013641.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM82	NM_001013641.3	MANE Select	c.692C>T	p.Ser231Leu	missense	Exon 4 of 6	NP_001013663.1
	SLC25A34-AS1	NR_149050.1		n.462-4293G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM82	ENST00000375782.2	TSL:1 MANE Select	c.692C>T	p.Ser231Leu	missense	Exon 4 of 6	ENSP00000364938.1
	TMEM82	ENST00000853368.1		c.336+1321C>T		intron	N/A	ENSP00000523427.1
	TMEM82	ENST00000465575.1	TSL:5	n.632C>T		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes AF: 0.00510 AC: 776 AN: 152250 Hom.: 5 Cov.: 33

Gnomad AFR AF: 0.0175

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00203

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00335

GnomAD2 exomes AF: 0.00127 AC: 316 AN: 248620 AF XY: 0.000881

Gnomad AFR exome AF: 0.0164

Gnomad AMR exome AF: 0.00107

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000107

Gnomad OTH exome AF: 0.000659

GnomAD4 exome AF: 0.000579 AC: 845 AN: 1460208 Hom.: 12 Cov.: 32 AF XY: 0.000500 AC XY: 363 AN XY: 726328

African (AFR) AF: 0.0185 AC: 621 AN: 33480

American (AMR) AF: 0.00125 AC: 56 AN: 44664

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86098

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52158

Middle Eastern (MID) AF: 0.00156 AC: 9 AN: 5766

European-Non Finnish (NFE) AF: 0.0000854 AC: 95 AN: 1111850

Other (OTH) AF: 0.00101 AC: 61 AN: 60374

GnomAD4 genome AF: 0.00511 AC: 778 AN: 152368 Hom.: 5 Cov.: 33 AF XY: 0.00518 AC XY: 386 AN XY: 74518

African (AFR) AF: 0.0175 AC: 727 AN: 41590

American (AMR) AF: 0.00203 AC: 31 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68034

Other (OTH) AF: 0.00331 AC: 7 AN: 2114

Alfa AF: 0.00175 Hom.: 4

Bravo AF: 0.00569

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.0168 AC: 74

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00154 AC: 187

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.36
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.040	T
Eigen	Pathogenic	0.74
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.86	D
MetaRNN	Benign	0.0085	T
MetaSVM	Benign	-0.56	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		4.8
PrimateAI	Benign	0.39	T
PROVEAN	Pathogenic	-4.4	D
REVEL	Benign	0.27
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.0070	D
Polyphen		1.0	D
Vest4		0.42
MVP		0.59
MPC		0.39
ClinPred		0.038	T
GERP RS		5.3
Varity_R		0.37
gMVP		0.54
Mutation Taster		=92/8	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: rs59905655; hg19: chr1-16071010; COSMIC: COSV99037489; COSMIC: COSV99037489;