rs1046542

Positions:

• chr1-203024763-A-G

Variant summary

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

The NM_138391.6(TMEM183A):​c.*1723A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 152,224 control chromosomes in the GnomAD database, including 2,236 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 0.16 (2236 hom., cov: 32)
  • Exomes 𝑓: 0.38 (0 hom.)
• Consequence: TMEM183A NM_138391.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.82

Genes affected

TMEM183A (HGNC:20173): (transmembrane protein 183A) Predicted to be involved in regulation of protein stability. Predicted to be integral component of membrane. Predicted to be part of SCF ubiquitin ligase complex. [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=-0.76).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM183A	NM_138391.6	c.*1723A>G		3_prime_UTR_variant	8/8	ENST00000367242.4	NP_612400.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM183A	ENST00000367242.4	c.*1723A>G		3_prime_UTR_variant	8/8	1	NM_138391.6	ENSP00000356211	P1

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23631 AN: 152098 Hom.: 2237 Cov.: 32

Gnomad AFR AF: 0.0507

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.270

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.147

GnomAD4 exome AF: 0.375 AC: 3 AN: 8 Hom.: 0 Cov.: 0 AF XY: 0.375 AC XY: 3 AN XY: 8

Gnomad4 ASJ exome AF: 0.00

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.155 AC: 23636 AN: 152216 Hom.: 2236 Cov.: 32 AF XY: 0.157 AC XY: 11679 AN XY: 74420

Gnomad4 AFR AF: 0.0506

Gnomad4 AMR AF: 0.146

Gnomad4 ASJ AF: 0.132

Gnomad4 EAS AF: 0.181

Gnomad4 SAS AF: 0.200

Gnomad4 FIN AF: 0.270

Gnomad4 NFE AF: 0.202

Gnomad4 OTH AF: 0.145

Alfa AF: 0.179 Hom.: 1111

Bravo AF: 0.144

Asia WGS AF: 0.180 AC: 626 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.18
DANN	Benign	0.72

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: rs1046542; hg19: chr1-202993891;