1-41017814-C-A

Variant names:

• chr1-41017814-C-A
• rs138195003
• NM_144990.4:c.778G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_144990.4(SLFNL1):​c.778G>T​(p.Val260Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000025 in 1,599,168 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V260M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SLFNL1 NM_144990.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.32
• Publications: 8 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144990.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLFNL1	NM_144990.4	MANE Select	c.778G>T	p.Val260Leu	missense	Exon 4 of 6	NP_659427.3
	SLFNL1	NM_001168247.3		c.778G>T	p.Val260Leu	missense	Exon 4 of 6	NP_001161719.1	Q499Z3-1
	SLFNL1	NM_001377532.1		c.778G>T	p.Val260Leu	missense	Exon 2 of 4	NP_001364461.1	Q499Z3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLFNL1	ENST00000302946.13	TSL:1 MANE Select	c.778G>T	p.Val260Leu	missense	Exon 4 of 6	ENSP00000304401.8	Q499Z3-1
	SLFNL1	ENST00000359345.5	TSL:1	c.778G>T	p.Val260Leu	missense	Exon 2 of 4	ENSP00000352299.1	Q499Z3-1
	SLFNL1-AS1	ENST00000626479.1	TSL:1	n.3225C>A		non_coding_transcript_exon	Exon 1 of 4

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152228 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000409 AC: 1 AN: 244344 AF XY: 0.00000757

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000908

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000207 AC: 3 AN: 1446822 Hom.: 0 Cov.: 31 AF XY: 0.00000279 AC XY: 2 AN XY: 717076

African (AFR) AF: 0.00 AC: 0 AN: 33274

American (AMR) AF: 0.00 AC: 0 AN: 44214

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25484

East Asian (EAS) AF: 0.00 AC: 0 AN: 39334

South Asian (SAS) AF: 0.00 AC: 0 AN: 85086

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52584

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5706

European-Non Finnish (NFE) AF: 0.00000272 AC: 3 AN: 1101474

Other (OTH) AF: 0.00 AC: 0 AN: 59666

GnomAD4 genome AF: 0.00000656 AC: 1 AN: 152346 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74490

African (AFR) AF: 0.00 AC: 0 AN: 41586

American (AMR) AF: 0.00 AC: 0 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2114

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.64
BayesDel_addAF	Benign	-0.039	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0066	T
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.020	T
MetaRNN	Uncertain	0.67	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L
PhyloP100		5.3
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.97	N
REVEL	Benign	0.18
Sift	Benign	0.073	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.92	P
Vest4		0.61
MutPred		0.60		Loss of sheet (P = 0.1398)
MVP		0.23
MPC		0.30
ClinPred		0.95	D
GERP RS		5.4
Varity_R		0.13
gMVP		0.62
Mutation Taster		=81/19	polymorphism

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

Other links and lift over

dbSNP: rs138195003; hg19: chr1-41483486;