rs374565633

Variant names:

• chr1-41017295-C-A
• rs374565633
• NM_144990.4:c.1040G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-41017295-C-A
• chr1-41017295-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_144990.4(SLFNL1):​c.1040G>T​(p.Arg347Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000479 in 1,460,458 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R347Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: SLFNL1 NM_144990.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.07

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.757

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLFNL1	NM_144990.4	c.1040G>T	p.Arg347Leu	missense_variant	Exon 5 of 6	ENST00000302946.13	NP_659427.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLFNL1	ENST00000302946.13	c.1040G>T	p.Arg347Leu	missense_variant	Exon 5 of 6	1	NM_144990.4	ENSP00000304401.8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000242 AC: 6 AN: 248168 Hom.: 0 AF XY: 0.0000298 AC XY: 4 AN XY: 134314

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000535

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1460458 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 726478

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: 0.00000540

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000412 AC: 5

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.82
BayesDel_addAF	Uncertain	0.073	D
BayesDel_noAF	Uncertain	0.020
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	T;T;.;T
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.73	.;T;T;.
M_CAP	Benign	0.061	D
MetaRNN	Pathogenic	0.76	D;D;D;D
MetaSVM	Uncertain	-0.16	T
MutationAssessor	Uncertain	2.7	M;M;.;M
PrimateAI	Benign	0.48	T
PROVEAN	Pathogenic	-5.1	D;D;D;D
REVEL	Uncertain	0.50
Sift	Uncertain	0.0070	D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		0.83	P;P;P;P
Vest4		0.85
MutPred		0.68		Gain of catalytic residue at R347 (P = 0.0466);Gain of catalytic residue at R347 (P = 0.0466);.;Gain of catalytic residue at R347 (P = 0.0466);
MVP		0.62
MPC		0.29
ClinPred		0.83	D
GERP RS		5.6
Varity_R		0.44
gMVP		0.74

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: rs374565633; hg19: chr1-41482967;