chr17-35441019-G-T

Position:

• chr17-35441019-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_144682.6(SLFN13):​c.2270C>A​(p.Pro757His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLFN13 NM_144682.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.22

Genes affected

SLFN13 (HGNC:26481): (schlafen family member 13) Enables endoribonuclease activity. Involved in rRNA catabolic process and tRNA catabolic process. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34960675).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLFN13	NM_144682.6	c.2270C>A	p.Pro757His	missense_variant	6/6	ENST00000285013.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLFN13	ENST00000285013.11	c.2270C>A	p.Pro757His	missense_variant	6/6	1	NM_144682.6	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Sep 16, 2021

The c.2270C>A (p.P757H) alteration is located in exon 6 (coding exon 4) of the SLFN13 gene. This alteration results from a C to A substitution at nucleotide position 2270, causing the proline (P) at amino acid position 757 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	0.28
BayesDel_addAF	Benign	-0.098	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.20	T;T;T;.;T
Eigen	Uncertain	0.21
Eigen_PC	Benign	0.0044
FATHMM_MKL	Benign	0.40	N
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.35	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.8	M;M;M;.;M
MutationTaster	Benign	0.57	N;N;N;N;N;N
PrimateAI	Benign	0.34	T
PROVEAN	Pathogenic	-5.4	D;D;D;D;.
REVEL	Benign	0.069
Sift	Pathogenic	0.0	D;D;D;D;.
Sift4G	Pathogenic	0.0010	D;D;D;D;D
Polyphen		1.0	D;D;D;D;D
Vest4		0.24
MutPred		0.54		Loss of stability (P = 0.0641);Loss of stability (P = 0.0641);Loss of stability (P = 0.0641);.;Loss of stability (P = 0.0641);
MVP		0.40
MPC		0.29
ClinPred		1.0	D
GERP RS		3.4
Varity_R		0.42
gMVP		0.18

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: rs773745875; hg19: chr17-33768038;