Variant chr14-24189654-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The ENST00000261789.9(TM9SF1):c.1582G>A(p.Asp528Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TM9SF1
ENST00000261789.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.41

Variant links:

Genes affected

TM9SF1 (HGNC:11864): (transmembrane 9 superfamily member 1) Predicted to be involved in protein localization to membrane. Predicted to be located in autophagosome membrane; cytoplasmic vesicle; and lysosomal membrane. Predicted to be integral component of membrane. Predicted to be active in membrane. [provided by Alliance of Genome Resources, Apr 2022]

TM9SF1 links:

ENSG00000254692 (HGNC:):

ENSG00000254692 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.867

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TM9SF1	NM_006405.7 linkuse as main transcript	c.1582G>A	p.Asp528Asn	missense_variant	6/6	ENST00000261789.9	NP_006396.2	O15321-1
TM9SF1	NM_001289006.2 linkuse as main transcript	c.1321G>A	p.Asp441Asn	missense_variant	6/6		NP_001275935.1	O15321G3V1B9B4E3A9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TM9SF1	ENST00000261789.9 linkuse as main transcript	c.1582G>A	p.Asp528Asn	missense_variant	6/6	1	NM_006405.7	ENSP00000261789.4	O15321-1
ENSG00000254692	ENST00000530611.1 linkuse as main transcript	c.2209G>A	p.Asp737Asn	missense_variant	10/10	2		ENSP00000433967.1	E9PSI1
ENSG00000259522	ENST00000561419.1 linkuse as main transcript	n.190G>A		non_coding_transcript_exon_variant	2/31	2		ENSP00000454374.1	H3BMG7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461892

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 06, 2021

The c.1582G>A (p.D528N) alteration is located in exon 6 (coding exon 5) of the TM9SF1 gene. This alteration results from a G to A substitution at nucleotide position 1582, causing the aspartic acid (D) at amino acid position 528 to be replaced by an asparagine (N). 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

Pathogenic

0.74

BayesDel_addAF

Benign

-0.055

BayesDel_noAF

Benign

-0.32

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.12

T;.;.;.

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Uncertain

0.94

M_CAP

Uncertain

0.15

MetaRNN

Pathogenic

0.87

D;D;D;D

MetaSVM

Benign

-0.59

MutationAssessor

Benign

1.6

L;.;.;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Pathogenic

0.80

PROVEAN

Pathogenic

-4.6

D;D;D;D

REVEL

Uncertain

0.31

Sift

Uncertain

0.0020

D;D;D;.

Sift4G

Uncertain

0.023

D;D;D;D

Polyphen

0.77

P;.;.;.

Vest4

0.73

MutPred

0.81

Gain of MoRF binding (P = 0.0405);.;.;.;

MVP

0.66

MPC

1.3

ClinPred

0.99

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.78

gMVP

0.72

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over