chr1-160612534-G-A

Position:

• chr1-160612534-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_003037.5(SLAMF1):​c.911C>T​(p.Thr304Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: SLAMF1 NM_003037.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.80

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4067649).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLAMF1	NM_003037.5	c.911C>T	p.Thr304Ile	missense_variant	6/7	ENST00000302035.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLAMF1	ENST00000302035.11	c.911C>T	p.Thr304Ile	missense_variant	6/7	1	NM_003037.5	P1
SLAMF1	ENST00000538290.2	c.994C>T	p.Pro332Ser	missense_variant	7/8	1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

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

Nov 02, 2023

The c.911C>T (p.T304I) alteration is located in exon 6 (coding exon 6) of the SLAMF1 gene. This alteration results from a C to T substitution at nucleotide position 911, causing the threonine (T) at amino acid position 304 to be replaced by an isoleucine (I). 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	0.61
BayesDel_addAF	Pathogenic	0.36	D
BayesDel_noAF	Uncertain	-0.030
CADD	Pathogenic	26
DANN	Uncertain	1.0
Eigen	Pathogenic	0.73
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.041	D
MetaRNN	Benign	0.41	T
MutationTaster	Benign	0.99	D;D;D
Vest4		0.39
MVP		0.70
ClinPred		0.98	D
GERP RS		4.3
gMVP		0.15

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-160582324;