Variant chr17-35478122-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.1229G>A(p.Arg410His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000447 in 1,545,026 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 (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000047 ( 0 hom. )

Consequence

SLFN12L
NM_001363830.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -4.07

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:

(HGNC:):

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=0.038013697).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLFN12L	NM_001363830.2 linkuse as main transcript	c.1229G>A	p.Arg410His	missense_variant	4/5	ENST00000628453.4
SLFN12L	NM_001195790.3 linkuse as main transcript	c.1103G>A	p.Arg368His	missense_variant	5/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLFN12L	ENST00000628453.4 linkuse as main transcript	c.1229G>A	p.Arg410His	missense_variant	4/5	5	NM_001363830.2	A2
	ENST00000587076.1 linkuse as main transcript	n.129C>T		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000211

AC:

AN:

156422

Hom.:

AF XY:

0.000169

AC XY:

AN XY:

82724

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00123

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000133

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000474

AC:

AN:

1392898

Hom.:

Cov.:

AF XY:

0.0000466

AC XY:

AN XY:

687292

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000984

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000165

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000158

Gnomad4 OTH exome

AF:

0.0000173

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152128

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74306

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.000110

ExAC

AF:

0.0000789

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

Dec 21, 2022

The c.1157G>A (p.R386H) alteration is located in exon 3 (coding exon 3) of the SLFN12L gene. This alteration results from a G to A substitution at nucleotide position 1157, causing the arginine (R) at amino acid position 386 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

0.096

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.52

DANN

Benign

0.15

DEOGEN2

Benign

0.063

T;.;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.00088

LIST_S2

Benign

0.61

T;T;.

M_CAP

Benign

0.0014

MetaRNN

Benign

0.038

T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.34

N;.;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.29

PROVEAN

Benign

0.84

N;N;.

REVEL

Benign

0.15

Sift

Benign

0.23

T;T;.

Sift4G

Benign

0.62

T;T;T

Polyphen

0.0010

.;B;.

Vest4

0.049

MutPred

0.34

.;Loss of helix (P = 0.028);.;

MVP

0.014

MPC

0.025

ClinPred

0.020

GERP RS

-1.9

Varity_R

0.018

gMVP

0.10

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.16

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