rs3091242

Positions:

• chr1-25348294-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

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 = 0.539 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM50A	NM_014313.4	c.207-3332C>T		intron_variant		ENST00000374358.5	NP_055128.1
TMEM50A	XM_005245817.1	c.207-3332C>T		intron_variant			XP_005245874.1
TMEM50A	XM_011541159.3	c.207-3332C>T		intron_variant			XP_011539461.1
TMEM50A	XM_047416632.1	c.207-3332C>T		intron_variant			XP_047272588.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM50A	ENST00000374358.5	c.207-3332C>T		intron_variant		1	NM_014313.4	ENSP00000363478	P1

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

Gnomad4 AFR AF: 0.249

Gnomad4 AMR AF: 0.463

Gnomad4 ASJ AF: 0.452

Gnomad4 EAS AF: 0.281

Gnomad4 SAS AF: 0.328

Gnomad4 FIN AF: 0.515

Gnomad4 NFE AF: 0.544

Gnomad4 OTH AF: 0.429

Alfa AF: 0.512 Hom.: 20061

Bravo AF: 0.422

Asia WGS AF: 0.282 AC: 980 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	8.3
DANN	Benign	0.74

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: rs3091242; hg19: chr1-25674785;