17-35475209-T-C

Variant summary

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

The NM_001363830.2(SLFN12L):ā€‹c.1553A>Gā€‹(p.Gln518Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000248 in 1,614,112 control chromosomes in the GnomAD database, including 1 homozygotes. 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 (ā˜…).

Frequency

Genomes: š‘“ 0.00017 ( 0 hom., cov: 31)
Exomes š‘“: 0.00026 ( 1 hom. )

Consequence

SLFN12L
NM_001363830.2 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -4.68
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]

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=0.012334853).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SLFN12LNM_001363830.2 linkuse as main transcriptc.1553A>G p.Gln518Arg missense_variant 5/5 ENST00000628453.4
SLFN12LNM_001195790.3 linkuse as main transcriptc.1427A>G p.Gln476Arg missense_variant 6/6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SLFN12LENST00000628453.4 linkuse as main transcriptc.1553A>G p.Gln518Arg missense_variant 5/55 NM_001363830.2 A2
SLFN12LENST00000260908.13 linkuse as main transcriptc.1427A>G p.Gln476Arg missense_variant 4/45 P2
SLFN12LENST00000587436.1 linkuse as main transcriptn.395+2866A>G intron_variant, non_coding_transcript_variant 2
SLFN12LENST00000590802.1 linkuse as main transcriptn.152+2866A>G intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
AF:
0.000171
AC:
26
AN:
152224
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000483
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:
0.000188
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000247
AC:
62
AN:
251070
Hom.:
0
AF XY:
0.000309
AC XY:
42
AN XY:
135866
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000202
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000163
Gnomad FIN exome
AF:
0.0000924
Gnomad NFE exome
AF:
0.000414
Gnomad OTH exome
AF:
0.000164
GnomAD4 exome
AF:
0.000256
AC:
374
AN:
1461888
Hom.:
1
Cov.:
31
AF XY:
0.000252
AC XY:
183
AN XY:
727244
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.000179
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000128
Gnomad4 FIN exome
AF:
0.000206
Gnomad4 NFE exome
AF:
0.000299
Gnomad4 OTH exome
AF:
0.000166
GnomAD4 genome
AF:
0.000171
AC:
26
AN:
152224
Hom.:
0
Cov.:
31
AF XY:
0.000161
AC XY:
12
AN XY:
74372
show subpopulations
Gnomad4 AFR
AF:
0.0000483
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000188
Gnomad4 NFE
AF:
0.000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000357
Hom.:
0
Bravo
AF:
0.000121
TwinsUK
AF:
0.000539
AC:
2
ALSPAC
AF:
0.00
AC:
0
ExAC
AF:
0.000255
AC:
31
EpiCase
AF:
0.000872
EpiControl
AF:
0.000593

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 submitterclinical testingAmbry GeneticsOct 03, 2022The c.1481A>G (p.Q494R) alteration is located in exon 4 (coding exon 4) of the SLFN12L gene. This alteration results from a A to G substitution at nucleotide position 1481, causing the glutamine (Q) at amino acid position 494 to be replaced by an arginine (R). 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
0.070
BayesDel_addAF
Benign
-0.60
T
BayesDel_noAF
Benign
-0.78
CADD
Benign
0.0020
DANN
Benign
0.13
DEOGEN2
Benign
0.025
T;.;T
Eigen
Benign
-2.7
Eigen_PC
Benign
-2.7
FATHMM_MKL
Benign
0.0015
N
LIST_S2
Benign
0.47
T;T;.
M_CAP
Benign
0.0014
T
MetaRNN
Benign
0.012
T;T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
-0.90
N;.;.
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.25
T
PROVEAN
Benign
0.060
N;N;.
REVEL
Benign
0.020
Sift
Benign
0.46
T;T;.
Sift4G
Benign
0.41
T;T;T
Polyphen
0.0
.;B;.
Vest4
0.029
MVP
0.014
MPC
0.023
ClinPred
0.018
T
GERP RS
-4.8
Varity_R
0.021
gMVP
0.095

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.

Other links and lift over

dbSNP: rs200292758; hg19: chr17-33802228; API