Genetic Variant NM_017854.2:c.70C>T (chr19-47048545-G-A) – 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_017854.2(TMEM160):c.70C>T(p.Pro24Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000296 in 1,352,724 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000030 ( 0 hom. )

Consequence

TMEM160
NM_017854.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.03

Publications

0 publications found

Variant links:

Genes affected

TMEM160 (HGNC:26042): (transmembrane protein 160) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM160 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=0.1365856).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM160	NM_017854.2 link	c.70C>T	p.Pro24Ser	missense_variant	Exon 1 of 3	ENST00000253047.7	NP_060324.1	Q9NX00

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM160	ENST00000253047.7 link	c.70C>T	p.Pro24Ser	missense_variant	Exon 1 of 3	1	NM_017854.2	ENSP00000253047.5		Q9NX00

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000296

AC:

AN:

1352724

Hom.:

Cov.:

AF XY:

0.00000450

AC XY:

AN XY:

667154

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27814

American (AMR)

AF:

0.0000310

AC:

AN:

32274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24084

East Asian (EAS)

AF:

0.00

AC:

AN:

31606

South Asian (SAS)

AF:

0.00

AC:

AN:

76566

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33438

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3980

European-Non Finnish (NFE)

AF:

0.00000281

AC:

AN:

1066648

Other (OTH)

AF:

0.00

AC:

AN:

56314

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

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 17, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.70C>T (p.P24S) alteration is located in exon 1 (coding exon 1) of the TMEM160 gene. This alteration results from a C to T substitution at nucleotide position 70, causing the proline (P) at amino acid position 24 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.46

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0098

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.085

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Benign

0.61

M_CAP

Pathogenic

0.41

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PhyloP100

3.0

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-1.1

REVEL

Benign

0.024

Sift

Benign

0.071

Sift4G

Benign

0.53

Polyphen

0.018

Vest4

0.21

MutPred

0.27

Loss of catalytic residue at P24 (P = 0.0036);

MVP

0.13

MPC

2.0

ClinPred

0.59

GERP RS

3.5

PromoterAI

-0.028

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.2

Varity_R

0.077

gMVP

0.50

Mutation Taster

=91/9

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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NM_017854.2:c.70C>T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over