Genetic Variant NM_025124.4:c.272A>C (chr11-67467558-T-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_025124.4(TMEM134):c.272A>C(p.Gln91Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,808 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TMEM134
NM_025124.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.00

Publications

0 publications found

Variant links:

Genes affected

TMEM134 (HGNC:26142): (transmembrane protein 134) Located in cytosol and perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TMEM134 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.22271997).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025124.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TMEM134	NM_025124.4	MANE Select	c.272A>C	p.Gln91Pro	missense	Exon 3 of 7	NP_079400.1	Q9H6X4-1
TMEM134	NM_001078651.3		c.245A>C	p.Gln82Pro	missense	Exon 3 of 7	NP_001072119.1
TMEM134	NM_001078650.3		c.272A>C	p.Gln91Pro	missense	Exon 3 of 6	NP_001072118.1	Q9H6X4-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TMEM134	ENST00000308022.7	TSL:2 MANE Select	c.272A>C	p.Gln91Pro	missense	Exon 3 of 7	ENSP00000312615.2	Q9H6X4-1
TMEM134	ENST00000393877.3	TSL:1	c.272A>C	p.Gln91Pro	missense	Exon 3 of 6	ENSP00000377455.3	Q9H6X4-2
TMEM134	ENST00000501408.6	TSL:1	n.327A>C		non_coding_transcript_exon	Exon 3 of 4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461808

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727200

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53392

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5728

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1112006

Other (OTH)

AF:

0.00

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

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

0.17

BayesDel_addAF

Uncertain

0.027

BayesDel_noAF

Benign

-0.20

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.033

Eigen

Uncertain

0.27

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Benign

0.51

LIST_S2

Benign

0.84

M_CAP

Benign

0.028

MetaRNN

Benign

0.22

MetaSVM

Benign

-0.49

MutationAssessor

Benign

1.4

PhyloP100

2.0

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-0.97

REVEL

Benign

0.14

Sift

Benign

0.038

Sift4G

Benign

0.11

Polyphen

0.71

Vest4

0.43

MutPred

0.50

Loss of sheet (P = 0.0181)

MVP

0.18

MPC

0.41

ClinPred

0.80

GERP RS

4.4

PromoterAI

-0.046

Neutral

(source)

Varity_R

0.38

gMVP

0.64

Mutation Taster

=80/20

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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