NM_144990.4:c.-76C>T

Variant names:

• chr1-41020736-G-A
• rs3738369
• NM_144990.4:c.-76C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_144990.4(SLFNL1):​c.-76C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 1,398,696 control chromosomes in the GnomAD database, including 11,379 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.11 (1240 hom., cov: 32)
  • Exomes 𝑓: 0.12 (10139 hom.)
• Consequence: SLFNL1 NM_144990.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.197
• Publications: 14 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

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.-76C>T		5_prime_UTR	Exon 3 of 6	NP_659427.3
	SLFNL1	NM_001168247.3		c.-76C>T		5_prime_UTR	Exon 3 of 6	NP_001161719.1	Q499Z3-1
	SLFNL1	NM_001377532.1		c.-76C>T		5_prime_UTR	Exon 1 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.-76C>T		5_prime_UTR	Exon 3 of 6	ENSP00000304401.8	Q499Z3-1
	SLFNL1	ENST00000359345.5	TSL:1	c.-76C>T		5_prime_UTR	Exon 1 of 4	ENSP00000352299.1	Q499Z3-1
	SLFNL1-AS1	ENST00000626479.1	TSL:1	n.3812+2335G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16130 AN: 152020 Hom.: 1237 Cov.: 32

Gnomad AFR AF: 0.0301

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.276

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.126

GnomAD4 exome AF: 0.120 AC: 149088 AN: 1246558 Hom.: 10139 Cov.: 17 AF XY: 0.119 AC XY: 73663 AN XY: 618512

African (AFR) AF: 0.0256 AC: 739 AN: 28894

American (AMR) AF: 0.284 AC: 10536 AN: 37144

Ashkenazi Jewish (ASJ) AF: 0.114 AC: 2366 AN: 20832

East Asian (EAS) AF: 0.270 AC: 10144 AN: 37532

South Asian (SAS) AF: 0.113 AC: 8144 AN: 71978

European-Finnish (FIN) AF: 0.107 AC: 4351 AN: 40570

Middle Eastern (MID) AF: 0.111 AC: 474 AN: 4276

European-Non Finnish (NFE) AF: 0.111 AC: 105478 AN: 952634

Other (OTH) AF: 0.130 AC: 6856 AN: 52698

GnomAD4 genome AF: 0.106 AC: 16139 AN: 152138 Hom.: 1240 Cov.: 32 AF XY: 0.110 AC XY: 8171 AN XY: 74372

African (AFR) AF: 0.0300 AC: 1248 AN: 41538

American (AMR) AF: 0.236 AC: 3618 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.114 AC: 394 AN: 3466

East Asian (EAS) AF: 0.277 AC: 1425 AN: 5150

South Asian (SAS) AF: 0.120 AC: 580 AN: 4824

European-Finnish (FIN) AF: 0.107 AC: 1134 AN: 10582

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.109 AC: 7415 AN: 67960

Other (OTH) AF: 0.125 AC: 263 AN: 2110

Alfa AF: 0.113 Hom.: 1449

Bravo AF: 0.113

Asia WGS AF: 0.172 AC: 595 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.6
DANN	Benign	0.44
PhyloP100		-0.20
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3738369; hg19: chr1-41486408; COSMIC: COSV57235990;