dbSNP rs3093642: TMEM50A:n.951C>T (chr1-25361251-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The ENST00000491936.5(TMEM50A):n.951C>T variant causes a non coding transcript exon 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
ENST00000491936.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.39

Publications

4 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

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=-0.84).

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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 67 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000491936.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM50A	NM_014313.4	MANE Select	c.*546C>T		3_prime_UTR	Exon 7 of 7	NP_055128.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
TMEM50A	ENST00000491936.5	TSL:1	n.951C>T	non_coding_transcript_exon	Exon 5 of 5
TMEM50A	ENST00000374358.5	TSL:1 MANE Select	c.*546C>T	3_prime_UTR	Exon 7 of 7	ENSP00000363478.4
TMEM50A	ENST00000480937.5	TSL:2	n.1074C>T	non_coding_transcript_exon	Exon 6 of 6

Frequencies

GnomAD3 genomes

AF:

0.0262

AC:

3991

AN:

152082

Hom.:

Cov.:

show subpopulations

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:

AN:

1312

Hom.:

Cov.:

AF XY:

0.0253

AC XY:

AN XY:

750

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.0103

AC:

AN:

194

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00877

AC:

AN:

114

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0284

AC:

AN:

914

Other (OTH)

AF:

0.0357

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.552

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0262

AC:

3990

AN:

152200

Hom.:

Cov.:

AF XY:

0.0257

AC XY:

1913

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.00691

AC:

287

AN:

41506

American (AMR)

AF:

0.0238

AC:

363

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.0611

AC:

212

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5192

South Asian (SAS)

AF:

0.0180

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0286

AC:

303

AN:

10598

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0389

AC:

2646

AN:

68008

Other (OTH)

AF:

0.0394

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

201

401

602

802

1003

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

150

200

250

<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:

0.0355

Hom.:

147

Bravo

AF:

0.0254

Asia WGS

AF:

0.00779

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

2.2

(source)

DANN

Benign

0.73

PhyloP100

-1.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism

(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

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over