rs764902822

Variant names:

• chr17-5214937-G-C
• rs764902822
• NM_207103.3:c.271C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_207103.3(SCIMP):​c.271C>G​(p.Leu91Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000208 in 1,444,136 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SCIMP NM_207103.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0390
• Publications: 0 publications found

Genes affected

SCIMP (HGNC:33504): (SLP adaptor and CSK interacting membrane protein) This gene encodes a transmembrane adaptor protein that is expressed in antigen-presenting cells and is localized in the immunologic synapse. The encoded protein is involved in major histocompatibility complex class II signal transduction and immune synapse formation. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Dec 2012]

ZNF594-DT (HGNC:55347): (ZNF594 divergent transcript)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07510215).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207103.3. 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
	SCIMP	NM_207103.3	MANE Select	c.271C>G	p.Leu91Val	missense	Exon 4 of 5	NP_996986.1	Q6UWF3-1
	SCIMP	NM_001271842.1		c.250C>G	p.Leu84Val	missense	Exon 4 of 5	NP_001258771.1	Q6UWF3-3
	SCIMP	NM_001319190.2		c.250C>G	p.Leu84Val	missense	Exon 4 of 5	NP_001306119.1	Q6UWF3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCIMP	ENST00000574081.6	TSL:1 MANE Select	c.271C>G	p.Leu91Val	missense	Exon 4 of 5	ENSP00000461269.1	Q6UWF3-1
	SCIMP	ENST00000399600.8	TSL:1	c.250C>G	p.Leu84Val	missense	Exon 4 of 5	ENSP00000382509.4	Q6UWF3-3
	ZNF594-DT	ENST00000571689.1	TSL:1	n.367-210G>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000801 AC: 2 AN: 249572 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000579

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000208 AC: 3 AN: 1444136 Hom.: 0 Cov.: 28 AF XY: 0.00000139 AC XY: 1 AN XY: 719392

African (AFR) AF: 0.00 AC: 0 AN: 33046

American (AMR) AF: 0.0000674 AC: 3 AN: 44522

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25894

East Asian (EAS) AF: 0.00 AC: 0 AN: 39296

South Asian (SAS) AF: 0.00 AC: 0 AN: 85920

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53096

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5708

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1097024

Other (OTH) AF: 0.00 AC: 0 AN: 59630

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000827 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	1.5
DANN	Benign	0.97
DEOGEN2	Benign	0.038	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.057	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.075	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PhyloP100		0.039
PrimateAI	Benign	0.23	T
REVEL	Benign	0.022
Sift4G	Benign	0.56	T
Polyphen		0.10	B
Vest4		0.18
MutPred		0.095		Loss of glycosylation at P89 (P = 0.1593)
MVP		0.067
MPC		0.41
ClinPred		0.044	T
GERP RS		-1.9
Varity_R		0.026
gMVP		0.029

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

Other links and lift over

dbSNP: rs764902822; hg19: chr17-5118232;