Variant chr17-35479281-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001363830.2(SLFN12L):c.1001T>A(p.Val334Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000117 in 1,590,788 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

SLFN12L
NM_001363830.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.94

Variant links:

Genes affected

SLFN12L (HGNC:33920): (schlafen family member 12 like) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLFN12L links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLFN12L	NM_001363830.2 linkuse as main transcript	c.1001T>A	p.Val334Glu	missense_variant	3/5	ENST00000628453.4
SLFN12L	NM_001195790.3 linkuse as main transcript	c.875T>A	p.Val292Glu	missense_variant	4/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLFN12L	ENST00000628453.4 linkuse as main transcript	c.1001T>A	p.Val334Glu	missense_variant	3/5	5	NM_001363830.2	A2
SLFN12L	ENST00000260908.13 linkuse as main transcript	c.875T>A	p.Val292Glu	missense_variant	2/4	5		P2

Frequencies

GnomAD3 genomes

AF:

0.000138

AC:

AN:

152130

Hom.:

Cov.:

show subpopulations

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:

0.000660

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000746

AC:

AN:

214362

Hom.:

AF XY:

0.0000694

AC XY:

AN XY:

115204

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000199

Gnomad NFE exome

AF:

0.000119

Gnomad OTH exome

AF:

0.000182

GnomAD4 exome

AF:

0.000115

AC:

165

AN:

1438658

Hom.:

Cov.:

AF XY:

0.000122

AC XY:

AN XY:

713866

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000241

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000421

Gnomad4 NFE exome

AF:

0.000126

Gnomad4 OTH exome

AF:

0.0000672

GnomAD4 genome

AF:

0.000138

AC:

AN:

152130

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000660

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000201

Hom.:

Bravo

AF:

0.0000604

ExAC

AF:

0.0000495

AC:

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

Nov 19, 2022

The c.929T>A (p.V310E) alteration is located in exon 2 (coding exon 2) of the SLFN12L gene. This alteration results from a T to A substitution at nucleotide position 929, causing the valine (V) at amino acid position 310 to be replaced by a glutamic acid (E). 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

0.86

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Pathogenic

0.16

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.65

D;.;T

Eigen

Benign

0.16

Eigen_PC

Benign

-0.10

FATHMM_MKL

Benign

0.48

LIST_S2

Benign

0.68

T;T;.

M_CAP

Benign

0.024

MetaRNN

Uncertain

0.67

D;D;D

MetaSVM

Benign

-0.63

MutationAssessor

Uncertain

2.4

M;.;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.53

PROVEAN

Pathogenic

-5.7

D;D;.

REVEL

Uncertain

0.37

Sift

Pathogenic

0.0

D;D;.

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

.;D;.

Vest4

0.74

MVP

0.56

MPC

0.22

ClinPred

0.77

GERP RS

2.5

Varity_R

0.53

gMVP

0.56

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over