rs1046542

Variant names:

• chr1-203024763-A-G
• rs1046542
• NM_138391.6:c.*1723A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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]

ENSG00000294186 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138391.6. 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
	TMEM183A	NM_138391.6	MANE Select	c.*1723A>G		3_prime_UTR	Exon 8 of 8	NP_612400.3
	TMEM183A	NR_136530.2		n.3110A>G		non_coding_transcript_exon	Exon 9 of 9
	TMEM183A	NR_136531.2		n.2923A>G		non_coding_transcript_exon	Exon 8 of 8

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM183A	ENST00000367242.4	TSL:1 MANE Select	c.*1723A>G		3_prime_UTR	Exon 8 of 8	ENSP00000356211.3
	ENSG00000294186	ENST00000721797.1		n.117-1596T>C		intron	N/A
	ENSG00000294186	ENST00000721798.1		n.359-469T>C		intron	N/A

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 2 AN: 4

Other (OTH) AF: 0.500 AC: 1 AN: 2

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

African (AFR) AF: 0.0506 AC: 2104 AN: 41556

American (AMR) AF: 0.146 AC: 2239 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.132 AC: 457 AN: 3472

East Asian (EAS) AF: 0.181 AC: 935 AN: 5172

South Asian (SAS) AF: 0.200 AC: 964 AN: 4826

European-Finnish (FIN) AF: 0.270 AC: 2856 AN: 10584

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.202 AC: 13710 AN: 67996

Other (OTH) AF: 0.145 AC: 307 AN: 2116

Alfa AF: 0.178 Hom.: 1665

Bravo AF: 0.144

Asia WGS AF: 0.180 AC: 626 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.18
DANN	Benign	0.72
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

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: rs1046542; hg19: chr1-202993891;