chr1-160610769-A-T

Position:

• chr1-160610769-A-T

Variant summary

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

The NM_003037.5(SLAMF1):​c.987T>A​(p.Ser329Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLAMF1 NM_003037.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.197

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]

SLAMF1 (HGNC:):

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
SLAMF1	NM_003037.5	c.987T>A	p.Ser329Arg	missense_variant	7/7	ENST00000302035.11	NP_003028.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLAMF1	ENST00000302035.11	c.987T>A	p.Ser329Arg	missense_variant	7/7	1	NM_003037.5	ENSP00000306190.6
SLAMF1	ENST00000538290.2	c.1070T>A	p.Val357Glu	missense_variant	8/8	1		ENSP00000438406.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

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 05, 2024

The c.987T>A (p.S329R) alteration is located in exon 7 (coding exon 7) of the SLAMF1 gene. This alteration results from a T to A substitution at nucleotide position 987, causing the serine (S) at amino acid position 329 to be replaced by an arginine (R). 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	0.83
BayesDel_addAF	Benign	0.0033	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T
Eigen	Benign	0.12
Eigen_PC	Benign	0.044
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.028	D
MetaRNN	Uncertain	0.49	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Pathogenic	3.0	M
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.21
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.53
MutPred		0.18		Loss of disorder (P = 0.0523);
MVP		0.79
MPC		0.84
ClinPred		0.90	D
GERP RS		0.67
Varity_R		0.33

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-160580559;