Variant 17-35474969-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001363830.2(SLFN12L):c.1793G>A(p.Arg598His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000132 in 1,552,818 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R598C) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

SLFN12L
NM_001363830.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.02

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.016118526).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLFN12L	NM_001363830.2 linkuse as main transcript	c.1793G>A	p.Arg598His	missense_variant	5/5	ENST00000628453.4
SLFN12L	NM_001195790.3 linkuse as main transcript	c.1667G>A	p.Arg556His	missense_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
SLFN12L	ENST00000628453.4 linkuse as main transcript	c.1793G>A	p.Arg598His	missense_variant	5/5	5	NM_001363830.2	A2
SLFN12L	ENST00000260908.13 linkuse as main transcript	c.1667G>A	p.Arg556His	missense_variant	4/4	5		P2
SLFN12L	ENST00000587436.1 linkuse as main transcript	n.395+3106G>A		intron_variant, non_coding_transcript_variant		2
SLFN12L	ENST00000590802.1 linkuse as main transcript	n.152+3106G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.000138

AC:

AN:

151844

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000968

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000947

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000105

AC:

AN:

161912

Hom.:

AF XY:

0.000105

AC XY:

AN XY:

85930

show subpopulations

Gnomad AFR exome

AF:

0.000115

Gnomad AMR exome

AF:

0.0000406

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000174

Gnomad SAS exome

AF:

0.0000858

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000173

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000131

AC:

184

AN:

1400856

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

691554

show subpopulations

Gnomad4 AFR exome

AF:

0.0000318

Gnomad4 AMR exome

AF:

0.0000282

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000279

Gnomad4 SAS exome

AF:

0.0000752

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000154

Gnomad4 OTH exome

AF:

0.000155

GnomAD4 genome

AF:

0.000138

AC:

AN:

151962

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74300

show subpopulations

Gnomad4 AFR

AF:

0.0000965

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000947

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000165

Hom.:

Bravo

AF:

0.000121

ExAC

AF:

0.0000463

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

Feb 21, 2024

The c.1721G>A (p.R574H) alteration is located in exon 4 (coding exon 4) of the SLFN12L gene. This alteration results from a G to A substitution at nucleotide position 1721, causing the arginine (R) at amino acid position 574 to be replaced by a histidine (H). 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

0.16

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.78

DANN

Benign

0.57

DEOGEN2

Benign

0.026

T;.;T

Eigen

Benign

-1.9

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.0013

LIST_S2

Benign

0.56

T;T;.

M_CAP

Benign

0.00099

MetaRNN

Benign

0.016

T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.0

N;.;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.030

N;N;.

REVEL

Benign

0.025

Sift

Benign

0.16

T;T;.

Sift4G

Benign

0.11

T;T;T

Polyphen

0.037

.;B;.

Vest4

0.14

MVP

0.014

MPC

0.025

ClinPred

0.0074

GERP RS

-1.2

Varity_R

0.041

gMVP

0.28

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