rs3796504

Positions:

• chr1-160610759-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003037.5(SLAMF1):​c.997C>A​(p.Pro333Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0803 in 1,611,012 control chromosomes in the GnomAD database, including 5,787 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.061 (380 hom., cov: 33)
  • Exomes 𝑓: 0.082 (5407 hom.)
• Consequence: SLAMF1 NM_003037.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.69

Genes affected

SLAMF1 (HGNC:10903): (signaling lymphocytic activation molecule family member 1) Enables SH2 domain binding activity and identical protein binding activity. Involved in several processes, including negative regulation of CD40 signaling pathway; negative regulation of cytokine production; and positive regulation of MAPK cascade. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0018964708).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0876 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLAMF1	NM_003037.5	c.997C>A	p.Pro333Thr	missense_variant	7/7	ENST00000302035.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLAMF1	ENST00000302035.11	c.997C>A	p.Pro333Thr	missense_variant	7/7	1	NM_003037.5	P1
SLAMF1	ENST00000538290.2			downstream_gene_variant		1

Frequencies

GnomAD3 genomes AF: 0.0615 AC: 9363 AN: 152186 Hom.: 382 Cov.: 33

Gnomad AFR AF: 0.0155

Gnomad AMI AF: 0.0921

Gnomad AMR AF: 0.0618

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.00365

Gnomad SAS AF: 0.0547

Gnomad FIN AF: 0.0666

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0895

Gnomad OTH AF: 0.0757

GnomAD3 exomes AF: 0.0699 AC: 17536 AN: 251018 Hom.: 819 AF XY: 0.0713 AC XY: 9669 AN XY: 135650

Gnomad AFR exome AF: 0.0129

Gnomad AMR exome AF: 0.0430

Gnomad ASJ exome AF: 0.120

Gnomad EAS exome AF: 0.000871

Gnomad SAS exome AF: 0.0575

Gnomad FIN exome AF: 0.0675

Gnomad NFE exome AF: 0.0961

Gnomad OTH exome AF: 0.0818

GnomAD4 exome AF: 0.0822 AC: 119946 AN: 1458708 Hom.: 5407 Cov.: 29 AF XY: 0.0819 AC XY: 59451 AN XY: 725792

Gnomad4 AFR exome AF: 0.0112

Gnomad4 AMR exome AF: 0.0452

Gnomad4 ASJ exome AF: 0.121

Gnomad4 EAS exome AF: 0.00774

Gnomad4 SAS exome AF: 0.0593

Gnomad4 FIN exome AF: 0.0713

Gnomad4 NFE exome AF: 0.0901

Gnomad4 OTH exome AF: 0.0783

GnomAD4 genome AF: 0.0614 AC: 9355 AN: 152304 Hom.: 380 Cov.: 33 AF XY: 0.0607 AC XY: 4519 AN XY: 74470

Gnomad4 AFR AF: 0.0154

Gnomad4 AMR AF: 0.0616

Gnomad4 ASJ AF: 0.123

Gnomad4 EAS AF: 0.00366

Gnomad4 SAS AF: 0.0543

Gnomad4 FIN AF: 0.0666

Gnomad4 NFE AF: 0.0895

Gnomad4 OTH AF: 0.0750

Alfa AF: 0.0868 Hom.: 1525

Bravo AF: 0.0606

ESP6500AA AF: 0.0175 AC: 77

ESP6500EA AF: 0.0888 AC: 764

ExAC AF: 0.0719 AC: 8731

Asia WGS AF: 0.0290 AC: 102 AN: 3478

EpiCase AF: 0.0927

EpiControl AF: 0.0939

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.46
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.81	T
MetaRNN	Benign	0.0019	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
MutationTaster	Benign	0.99	D;D;D
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.25
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.16
MPC		0.84
ClinPred		0.029	T
GERP RS		4.1
Varity_R		0.25

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs3796504; hg19: chr1-160580549; COSMIC: COSV52502577; COSMIC: COSV52502577;