chr1-25361251-C-T

Variant names:

• chr1-25361251-C-T
• rs3093642
• NM_014313.4:c.*546C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_014313.4(TMEM50A):​c.*546C>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 0.0262 in 153,512 control chromosomes in the GnomAD database, including 68 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 0.026 (67 hom., cov: 32)
  • Exomes 𝑓: 0.023 (1 hom.)
• Consequence: TMEM50A NM_014313.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39

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=-0.84).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0262 (3990/152200) while in subpopulation NFE AF= 0.0389 (2646/68008). AF 95% confidence interval is 0.0377. There are 67 homozygotes in gnomad4. There are 1913 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 67 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM50A	NM_014313.4	c.*546C>T		3_prime_UTR_variant	Exon 7 of 7	ENST00000374358.5	NP_055128.1
TMEM50A	XM_011541159.3	c.*546C>T		3_prime_UTR_variant	Exon 7 of 7		XP_011539461.1
TMEM50A	XM_005245817.1	c.*546C>T		3_prime_UTR_variant	Exon 6 of 6		XP_005245874.1
TMEM50A	XM_047416632.1	c.*546C>T		3_prime_UTR_variant	Exon 6 of 6		XP_047272588.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM50A	ENST00000374358.5	c.*546C>T		3_prime_UTR_variant	Exon 7 of 7	1	NM_014313.4	ENSP00000363478.4
TMEM50A	ENST00000491936.5	n.951C>T		non_coding_transcript_exon_variant	Exon 5 of 5	1
TMEM50A	ENST00000480937.5	n.1074C>T		non_coding_transcript_exon_variant	Exon 6 of 6	2

Frequencies

GnomAD3 genomes AF: 0.0262 AC: 3991 AN: 152082 Hom.: 67 Cov.: 32

Gnomad AFR AF: 0.00694

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0237

Gnomad ASJ AF: 0.0611

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0180

Gnomad FIN AF: 0.0286

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0389

Gnomad OTH AF: 0.0398

GnomAD4 exome AF: 0.0229 AC: 30 AN: 1312 Hom.: 1 Cov.: 0 AF XY: 0.0253 AC XY: 19 AN XY: 750

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0103

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00877

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0284

Gnomad4 OTH exome AF: 0.0357

GnomAD4 genome AF: 0.0262 AC: 3990 AN: 152200 Hom.: 67 Cov.: 32 AF XY: 0.0257 AC XY: 1913 AN XY: 74432

Gnomad4 AFR AF: 0.00691

Gnomad4 AMR AF: 0.0238

Gnomad4 ASJ AF: 0.0611

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0180

Gnomad4 FIN AF: 0.0286

Gnomad4 NFE AF: 0.0389

Gnomad4 OTH AF: 0.0394

Alfa AF: 0.0341 Hom.: 28

Bravo AF: 0.0254

Asia WGS AF: 0.00779 AC: 28 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.2
DANN	Benign	0.73
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs3093642; hg19: chr1-25687742;