Genetic Variant NM_001137560.2:c.73T>C (chr6-44270815-T-C) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001137560.2(TMEM151B):c.73T>C(p.Ser25Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 27)

Exomes 𝑓: 0.0000051 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TMEM151B
NM_001137560.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.360

Publications

0 publications found

Variant links:

Genes affected

TMEM151B (HGNC:21315): (transmembrane protein 151B) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM151B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.047590792).

BP6

Variant 6-44270815-T-C is Benign according to our data. Variant chr6-44270815-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2569564.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001137560.2. 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
	TMEM151B	NM_001137560.2	MANE Select	c.73T>C	p.Ser25Pro	missense	Exon 1 of 3	NP_001131032.1	Q8IW70-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM151B	ENST00000451188.7	TSL:5 MANE Select	c.73T>C	p.Ser25Pro	missense	Exon 1 of 3	ENSP00000393161.2	Q8IW70-1
	TMEM151B	ENST00000438774.2	TSL:3	c.73T>C	p.Ser25Pro	missense	Exon 1 of 3	ENSP00000409337.2	Q8IW70-2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

142316

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000511

AC:

AN:

978584

Hom.:

Cov.:

AF XY:

0.00000434

AC XY:

AN XY:

461350

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

19402

American (AMR)

AF:

0.00

AC:

AN:

5168

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

9784

East Asian (EAS)

AF:

0.00

AC:

AN:

16802

South Asian (SAS)

AF:

0.00

AC:

AN:

18614

European-Finnish (FIN)

AF:

0.00

AC:

AN:

14568

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2350

European-Non Finnish (NFE)

AF:

0.00000584

AC:

AN:

855524

Other (OTH)

AF:

0.00

AC:

AN:

36372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.545

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

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

142316

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

69546

African (AFR)

AF:

0.00

AC:

AN:

38582

American (AMR)

AF:

0.00

AC:

AN:

14576

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3340

East Asian (EAS)

AF:

0.00

AC:

AN:

4664

South Asian (SAS)

AF:

0.00

AC:

AN:

4556

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8988

Middle Eastern (MID)

AF:

0.00

AC:

AN:

278

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

64576

Other (OTH)

AF:

0.00

AC:

AN:

1938

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.052

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

(source)

DANN

Benign

0.69

DEOGEN2

Benign

0.0031

Eigen

Benign

-0.94

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.00058

LIST_S2

Benign

0.19

M_CAP

Benign

0.036

MetaRNN

Benign

0.048

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.0

PhyloP100

0.36

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

0.11

REVEL

Benign

0.041

Sift

Benign

0.15

Sift4G

Benign

0.41

Polyphen

0.0

Vest4

0.045

MutPred

0.17

Gain of loop (P = 0.0045)

MVP

0.040

ClinPred

0.048

GERP RS

3.1

PromoterAI

0.032

Neutral

(source)

Varity_R

0.12

gMVP

0.21

Mutation Taster

=86/14

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over