17-35259270-C-T

Position:

• chr17-35259270-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_144975.4(SLFN5):​c.580C>T​(p.His194Tyr) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLFN5 NM_144975.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0920

Genes affected

SLFN5 (HGNC:28286): (schlafen family member 5) Predicted to enable ATP binding activity. Predicted to be involved in cell differentiation. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23828298).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLFN5	NM_144975.4	c.580C>T	p.His194Tyr	missense_variant	2/5	ENST00000299977.9	NP_659412.3
SLFN5	NM_001330183.2	c.580C>T	p.His194Tyr	missense_variant	2/4		NP_001317112.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLFN5	ENST00000299977.9	c.580C>T	p.His194Tyr	missense_variant	2/5	1	NM_144975.4	ENSP00000299977.3
SLFN5	ENST00000592325.1	c.580C>T	p.His194Tyr	missense_variant	2/2	1		ENSP00000466984.1
SLFN5	ENST00000542451.1	c.580C>T	p.His194Tyr	missense_variant	2/4	2		ENSP00000440537.1

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

Sep 06, 2022

The c.580C>T (p.H194Y) alteration is located in exon 2 (coding exon 1) of the SLFN5 gene. This alteration results from a C to T substitution at nucleotide position 580, causing the histidine (H) at amino acid position 194 to be replaced by a tyrosine (Y). 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	0.10
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	12
DANN	Uncertain	0.99
DEOGEN2	Benign	0.031	T;.;.
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.21	T;T;T
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.24	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L;.;L
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-3.0	D;D;.
REVEL	Benign	0.11
Sift	Benign	0.11	T;T;.
Sift4G	Benign	0.70	T;T;T
Polyphen		1.0	D;D;P
Vest4		0.41
MutPred		0.45		Gain of phosphorylation at H194 (P = 0.0563);Gain of phosphorylation at H194 (P = 0.0563);Gain of phosphorylation at H194 (P = 0.0563);
MVP		0.21
MPC		0.080
ClinPred		0.48	T
GERP RS		3.5
Varity_R		0.11
gMVP		0.13

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-33586289;