chr17-35475352-G-T

Position:

• chr17-35475352-G-T

Variant summary

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

The NM_001363830.2(SLFN12L):​c.1410C>A​(p.Ser470Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLFN12L NM_001363830.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.676

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]

ACMG classification

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	c.1410C>A	p.Ser470Arg	missense_variant	5/5	ENST00000628453.4
SLFN12L	NM_001195790.3	c.1284C>A	p.Ser428Arg	missense_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLFN12L	ENST00000628453.4	c.1410C>A	p.Ser470Arg	missense_variant	5/5	5	NM_001363830.2	A2
SLFN12L	ENST00000260908.13	c.1284C>A	p.Ser428Arg	missense_variant	4/4	5		P2
SLFN12L	ENST00000587436.1	n.395+2723C>A		intron_variant, non_coding_transcript_variant		2
SLFN12L	ENST00000590802.1	n.152+2723C>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 12, 2024

The c.1338C>A (p.S446R) alteration is located in exon 4 (coding exon 4) of the SLFN12L gene. This alteration results from a C to A substitution at nucleotide position 1338, causing the serine (S) at amino acid position 446 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	Pathogenic	0.84
BayesDel_addAF	Benign	-0.083	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.57	D;.;T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.73	T;T;.
M_CAP	Benign	0.0024	T
MetaRNN	Uncertain	0.63	D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M;.;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-3.6	D;D;.
REVEL	Benign	0.19
Sift	Pathogenic	0.0	D;D;.
Sift4G	Benign	0.10	T;T;T
Polyphen		0.45	.;B;.
Vest4		0.52
MutPred		0.81		.;Gain of MoRF binding (P = 0.069);.;
MVP		0.12
MPC		0.19
ClinPred		0.63	D
GERP RS		0.090
Varity_R		0.27
gMVP		0.30

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

Other links and lift over

dbSNP: rs1913950395; hg19: chr17-33802371;