NM_014313.4:c.*705T>C

Variant names:

• chr1-25361410-T-C
• rs1053438
• NM_014313.4:c.*705T>C

Variant summary

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

The NM_014313.4(TMEM50A):​c.*705T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.394 in 152,028 control chromosomes in the GnomAD database, including 13,665 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 0.39 (13662 hom., cov: 32)
  • Exomes 𝑓: 0.31 (3 hom.)
• Consequence: TMEM50A NM_014313.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.52

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.696 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM50A	NM_014313.4	c.*705T>C		3_prime_UTR_variant	Exon 7 of 7	ENST00000374358.5	NP_055128.1
TMEM50A	XM_011541159.3	c.*705T>C		3_prime_UTR_variant	Exon 7 of 7		XP_011539461.1
TMEM50A	XM_005245817.1	c.*705T>C		3_prime_UTR_variant	Exon 6 of 6		XP_005245874.1
TMEM50A	XM_047416632.1	c.*705T>C		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.*705T>C		3_prime_UTR_variant	Exon 7 of 7	1	NM_014313.4	ENSP00000363478.4
TMEM50A	ENST00000491936.5	n.*145T>C		downstream_gene_variant		1
TMEM50A	ENST00000480937.5	n.*131T>C		downstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.395 AC: 59947 AN: 151856 Hom.: 13650 Cov.: 32

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.478

Gnomad AMR AF: 0.451

Gnomad ASJ AF: 0.541

Gnomad EAS AF: 0.716

Gnomad SAS AF: 0.671

Gnomad FIN AF: 0.486

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.452

Gnomad OTH AF: 0.431

GnomAD4 exome AF: 0.315 AC: 17 AN: 54 Hom.: 3 Cov.: 0 AF XY: 0.382 AC XY: 13 AN XY: 34

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 0.00

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.310

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.395 AC: 59958 AN: 151974 Hom.: 13662 Cov.: 32 AF XY: 0.404 AC XY: 30008 AN XY: 74288

Gnomad4 AFR AF: 0.167

Gnomad4 AMR AF: 0.452

Gnomad4 ASJ AF: 0.541

Gnomad4 EAS AF: 0.715

Gnomad4 SAS AF: 0.671

Gnomad4 FIN AF: 0.486

Gnomad4 NFE AF: 0.452

Gnomad4 OTH AF: 0.436

Alfa AF: 0.443 Hom.: 15685

Bravo AF: 0.380

Asia WGS AF: 0.677 AC: 2352 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.090
DANN	Benign	0.49

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: rs1053438; hg19: chr1-25687901; COSMIC: COSV53799214; COSMIC: COSV53799214;