rs6115686

Positions:

• chr20-2817680-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001167670.3(TMEM239):​c.*667C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0797 in 153,524 control chromosomes in the GnomAD database, including 1,295 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 0.080 (1295 hom., cov: 33)
  • Exomes 𝑓: 0.0055 (0 hom.)
• Consequence: TMEM239 NM_001167670.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.148

Genes affected

TMEM239 (HGNC:40044): (transmembrane protein 239) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.231 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM239	NM_001167670.3	c.*667C>T		3_prime_UTR_variant	2/2	ENST00000380585.2	NP_001161142.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM239	ENST00000380585.2	c.*667C>T		3_prime_UTR_variant	2/2	1	NM_001167670.3	ENSP00000369959	P1
TMEM239	ENST00000361033.1	c.*667C>T		3_prime_UTR_variant	2/2	2		ENSP00000354312

Frequencies

GnomAD3 genomes AF: 0.0803 AC: 12217 AN: 152134 Hom.: 1296 Cov.: 33

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0335

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.171

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.0138

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00413

Gnomad OTH AF: 0.0626

GnomAD4 exome AF: 0.00550 AC: 7 AN: 1272 Hom.: 0 Cov.: 0 AF XY: 0.00831 AC XY: 5 AN XY: 602

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00676

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.375

Gnomad4 SAS exome AF: 0.143

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0263

GnomAD4 genome AF: 0.0803 AC: 12225 AN: 152252 Hom.: 1295 Cov.: 33 AF XY: 0.0818 AC XY: 6089 AN XY: 74450

Gnomad4 AFR AF: 0.235

Gnomad4 AMR AF: 0.0334

Gnomad4 ASJ AF: 0.00461

Gnomad4 EAS AF: 0.170

Gnomad4 SAS AF: 0.106

Gnomad4 FIN AF: 0.0138

Gnomad4 NFE AF: 0.00413

Gnomad4 OTH AF: 0.0624

Alfa AF: 0.0384 Hom.: 119

Bravo AF: 0.0885

Asia WGS AF: 0.147 AC: 510 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.1
DANN	Benign	0.69

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: rs6115686; hg19: chr20-2798326;