1-160750382-T-G

Position:

• chr1-160750382-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_021181.5(SLAMF7):​c.728T>G​(p.Leu243Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,766 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: SLAMF7 NM_021181.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.286

Genes affected

SLAMF7 (HGNC:21394): (SLAM family member 7) Enables identical protein binding activity. Predicted to be involved in adaptive immune response. Predicted to act upstream of or within regulation of natural killer cell activation. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

SLAMF7 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.885

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLAMF7	NM_021181.5	c.728T>G	p.Leu243Arg	missense_variant	4/7	ENST00000368043.8	NP_067004.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLAMF7	ENST00000368043.8	c.728T>G	p.Leu243Arg	missense_variant	4/7	1	NM_021181.5	ENSP00000357022.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000410 AC: 6 AN: 1461766 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727190

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000450

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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

Dec 04, 2024

The c.728T>G (p.L243R) alteration is located in exon 4 (coding exon 4) of the SLAMF7 gene. This alteration results from a T to G substitution at nucleotide position 728, causing the leucine (L) at amino acid position 243 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	Uncertain	0.35
BayesDel_addAF	Benign	-0.023	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.48	.;T;.;.
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.56	T;T;T;T
M_CAP	Benign	0.0079	T
MetaRNN	Pathogenic	0.88	D;D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.0	.;M;.;M
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.5	.;N;N;N
REVEL	Uncertain	0.32
Sift	Benign	0.065	.;T;T;D
Sift4G	Uncertain	0.0030	D;D;D;D
Polyphen		0.99	D;D;D;.
Vest4		0.69
MutPred		0.74		.;Gain of sheet (P = 0.0043);.;Gain of sheet (P = 0.0043);
MVP		0.40
MPC		0.72
ClinPred		0.49	T
GERP RS		-0.53
Varity_R		0.30
gMVP		0.49

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

LitVar

Other links and lift over

dbSNP: rs1191911566; hg19: chr1-160720172;