1-41017691-A-G

Position:

• chr1-41017691-A-G

Variant summary

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

The NM_144990.4(SLFNL1):​c.901T>C​(p.Tyr301His) variant causes a missense change. The variant allele was found at a frequency of 0.00000843 in 1,423,096 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000084 (0 hom.)
• Consequence: SLFNL1 NM_144990.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.31

Genes affected

SLFNL1 (HGNC:26313): (schlafen like 1) Predicted to enable ATP binding activity. [provided by Alliance of Genome Resources, Apr 2022]

SLFNL1-AS1 (HGNC:44126): (SLFNL1 antisense RNA 1)

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	Protein	UniProt
SLFNL1	NM_144990.4	c.901T>C	p.Tyr301His	missense_variant	4/6	ENST00000302946.13	NP_659427.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLFNL1	ENST00000302946.13	c.901T>C	p.Tyr301His	missense_variant	4/6	1	NM_144990.4	ENSP00000304401.8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000843 AC: 12 AN: 1423096 Hom.: 0 Cov.: 31 AF XY: 0.00000854 AC XY: 6 AN XY: 702678

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: 0.0000110

Gnomad4 OTH exome AF: 0.00

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

Jul 14, 2024

The c.901T>C (p.Y301H) alteration is located in exon 4 (coding exon 2) of the SLFNL1 gene. This alteration results from a T to C substitution at nucleotide position 901, causing the tyrosine (Y) at amino acid position 301 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	Pathogenic	0.90
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.0
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.076	T;.;T;.;T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.69	.;T;T;T;.
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.72	D;D;D;D;D
MetaSVM	Benign	-0.65	T
MutationAssessor	Uncertain	2.4	M;M;M;.;M
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-3.5	D;D;D;D;D
REVEL	Benign	0.27
Sift	Benign	0.031	D;D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D;D
Polyphen		0.98	D;P;D;P;D
Vest4		0.63
MutPred		0.60		Gain of catalytic residue at L303 (P = 0.0473);Gain of catalytic residue at L303 (P = 0.0473);Gain of catalytic residue at L303 (P = 0.0473);.;Gain of catalytic residue at L303 (P = 0.0473);
MVP		0.16
MPC		0.26
ClinPred		0.98	D
GERP RS		5.2
Varity_R		0.25
gMVP		0.68

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: rs1357127594; hg19: chr1-41483363;