Genetic Variant TMEM50A:c.*705T>C (chr1-25361410-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.52

Publications

34 publications found

Variant links:

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]

TMEM50A links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_014313.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

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.*705T>C		3_prime_UTR	Exon 7 of 7	NP_055128.1	O95807

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TMEM50A	ENST00000374358.5	TSL:1 MANE Select	c.*705T>C	3_prime_UTR	Exon 7 of 7	ENSP00000363478.4	O95807
TMEM50A	ENST00000905340.1		c.*705T>C	3_prime_UTR	Exon 6 of 6	ENSP00000575399.1
TMEM50A	ENST00000951033.1		c.*705T>C	3_prime_UTR	Exon 8 of 8	ENSP00000621092.1

Frequencies

GnomAD3 genomes

AF:

0.395

AC:

59947

AN:

151856

Hom.:

13650

Cov.:

show subpopulations

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:

AN:

Hom.:

Cov.:

AF XY:

0.382

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.250

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.310

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.452

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.395

AC:

59958

AN:

151974

Hom.:

13662

Cov.:

AF XY:

0.404

AC XY:

30008

AN XY:

74288

show subpopulations

African (AFR)

AF:

0.167

AC:

6943

AN:

41480

American (AMR)

AF:

0.452

AC:

6888

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.541

AC:

1877

AN:

3468

East Asian (EAS)

AF:

0.715

AC:

3690

AN:

5162

South Asian (SAS)

AF:

0.671

AC:

3234

AN:

4820

European-Finnish (FIN)

AF:

0.486

AC:

5129

AN:

10554

Middle Eastern (MID)

AF:

0.466

AC:

136

AN:

292

European-Non Finnish (NFE)

AF:

0.452

AC:

30706

AN:

67924

Other (OTH)

AF:

0.436

AC:

920

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1702

3404

5106

6808

8510

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

588

1176

1764

2352

2940

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.421

Hom.:

22856

Bravo

AF:

0.380

Asia WGS

AF:

0.677

AC:

2352

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.090

(source)

DANN

Benign

0.49

PhyloP100

-1.5

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over