rs770925097

Variant names:

• chr17-35259217-T-A
• rs770925097
• NM_144975.4:c.527T>A

Your query was ambiguous. Multiple possible variants found:

• chr17-35259217-T-A
• chr17-35259217-T-C
• chr17-35259217-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_144975.4(SLFN5):​c.527T>A​(p.Phe176Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,796 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SLFN5 NM_144975.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.58

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.898

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLFN5	NM_144975.4	c.527T>A	p.Phe176Tyr	missense_variant	Exon 2 of 5	ENST00000299977.9	NP_659412.3
SLFN5	NM_001330183.2	c.527T>A	p.Phe176Tyr	missense_variant	Exon 2 of 4		NP_001317112.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLFN5	ENST00000299977.9	c.527T>A	p.Phe176Tyr	missense_variant	Exon 2 of 5	1	NM_144975.4	ENSP00000299977.3
SLFN5	ENST00000592325.1	c.527T>A	p.Phe176Tyr	missense_variant	Exon 2 of 2	1		ENSP00000466984.1
SLFN5	ENST00000542451.1	c.527T>A	p.Phe176Tyr	missense_variant	Exon 2 of 4	2		ENSP00000440537.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000400 AC: 1 AN: 250252 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135362

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461796 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727192

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T;.;.
Eigen	Benign	0.18
Eigen_PC	Benign	-0.048
FATHMM_MKL	Benign	0.47	N
LIST_S2	Benign	0.54	T;T;T
M_CAP	Benign	0.0067	T
MetaRNN	Pathogenic	0.90	D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M;.;M
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-2.6	D;D;.
REVEL	Benign	0.13
Sift	Uncertain	0.0050	D;D;.
Sift4G	Uncertain	0.015	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.51
MutPred		0.82		Gain of ubiquitination at K179 (P = 0.0853);Gain of ubiquitination at K179 (P = 0.0853);Gain of ubiquitination at K179 (P = 0.0853);
MVP		0.24
MPC		0.42
ClinPred		0.88	D
GERP RS		3.5
Varity_R		0.43
gMVP		0.25

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: rs770925097; hg19: chr17-33586236;