rs3091242

Variant names:

• chr1-25348294-C-T
• rs3091242
• NM_014313.4:c.207-3332C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014313.4(TMEM50A):​c.207-3332C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.434 in 152,012 control chromosomes in the GnomAD database, including 15,648 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 0.43 (15648 hom., cov: 32)
• Consequence: TMEM50A NM_014313.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.632
• Publications: 50 publications found

Genes affected

TMEM50A (HGNC:30590): (transmembrane protein 50A) This gene is located in the RH gene locus, between the RHD and RHCE genes. The function of its protein product is unknown; however, its sequence has potential transmembrane domains suggesting that it may be an integral membrane protein. Its position between the RH genes suggests that polymorphisms in this gene may be tightly linked to RH haplotypes and may contribute to selective pressure for or against certain RH haplotypes. [provided by RefSeq, Jul 2008]

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 = 0.539 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014313.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM50A	NM_014313.4	MANE Select	c.207-3332C>T		intron	N/A	NP_055128.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM50A	ENST00000374358.5	TSL:1 MANE Select	c.207-3332C>T		intron	N/A	ENSP00000363478.4
	TMEM50A	ENST00000491936.5	TSL:1	n.138-3332C>T		intron	N/A
	TMEM50A	ENST00000905340.1		c.207-3332C>T		intron	N/A	ENSP00000575399.1

Frequencies

GnomAD3 genomes AF: 0.434 AC: 65893 AN: 151894 Hom.: 15637 Cov.: 32

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.523

Gnomad AMR AF: 0.464

Gnomad ASJ AF: 0.452

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.515

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.544

Gnomad OTH AF: 0.433

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.434 AC: 65911 AN: 152012 Hom.: 15648 Cov.: 32 AF XY: 0.429 AC XY: 31909 AN XY: 74300

African (AFR) AF: 0.249 AC: 10326 AN: 41478

American (AMR) AF: 0.463 AC: 7076 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.452 AC: 1568 AN: 3466

East Asian (EAS) AF: 0.281 AC: 1454 AN: 5176

South Asian (SAS) AF: 0.328 AC: 1582 AN: 4818

European-Finnish (FIN) AF: 0.515 AC: 5426 AN: 10540

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.544 AC: 36954 AN: 67940

Other (OTH) AF: 0.429 AC: 906 AN: 2112

Alfa AF: 0.505 Hom.: 54060

Bravo AF: 0.422

Asia WGS AF: 0.282 AC: 980 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	8.3
DANN	Benign	0.74
PhyloP100		0.63
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: rs3091242; hg19: chr1-25674785;