rs59905655

chr1-15744515-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM82	NM_001013641.3	c.692C>T	p.Ser231Leu	missense_variant	4/6	ENST00000375782.2
SLC25A34-AS1	NR_149050.1	n.462-4293G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM82	ENST00000375782.2	c.692C>T	p.Ser231Leu	missense_variant	4/6	1	NM_001013641.3	P1
SLC25A34-AS1	ENST00000418525.2	n.468-4293G>A		intron_variant, non_coding_transcript_variant		3
TMEM82	ENST00000465575.1	n.632C>T		non_coding_transcript_exon_variant	3/3	5

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

GnomAD3 exomes AF: 0.00127 AC: 316 AN: 248620 Hom.: 1 AF XY: 0.000881 AC XY: 119 AN XY: 135022

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 SAS exome AF: 0.0000329

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

Gnomad4 AFR exome AF: 0.0185

Gnomad4 AMR exome AF: 0.00125

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000854

Gnomad4 OTH exome AF: 0.00101

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

Gnomad4 AFR AF: 0.0175

Gnomad4 AMR AF: 0.00203

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000132

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00133 Hom.: 1

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 v4.3

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
MutationTaster	Benign	0.96	D
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

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

Publications

LitVar

Other links and lift over

dbSNP: rs59905655; hg19: chr1-16071010; COSMIC: COSV99037489; COSMIC: COSV99037489;