17-5221317-T-C

Variant names:

• chr17-5221317-T-C
• rs1465184634
• NM_207103.3:c.179A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_207103.3(SCIMP):​c.179A>G​(p.His60Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,440 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: 6.8e-7 (0 hom.)
• Consequence: SCIMP NM_207103.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.393
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.057682663).

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.179A>G	p.His60Arg	missense	Exon 3 of 5	NP_996986.1	Q6UWF3-1
	SCIMP	NM_001271842.1		c.158A>G	p.His53Arg	missense	Exon 3 of 5	NP_001258771.1	Q6UWF3-3
	SCIMP	NM_001319190.2		c.158A>G	p.His53Arg	missense	Exon 3 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.179A>G	p.His60Arg	missense	Exon 3 of 5	ENSP00000461269.1	Q6UWF3-1
	SCIMP	ENST00000399600.8	TSL:1	c.158A>G	p.His53Arg	missense	Exon 3 of 5	ENSP00000382509.4	Q6UWF3-3
	ZNF594-DT	ENST00000571689.1	TSL:1	n.514-2000T>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461440 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727080

African (AFR) AF: 0.00 AC: 0 AN: 33466

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111622

Other (OTH) AF: 0.00 AC: 0 AN: 60374

GnomAD4 genome Cov.: 32

EpiCase AF: 0.0000545

EpiControl AF: 0.00

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	0.075
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	7.8
DANN	Benign	0.74
DEOGEN2	Benign	0.19	T
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.058	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.39
PrimateAI	Benign	0.28	T
REVEL	Benign	0.051
Sift4G	Benign	0.15	T
Polyphen		0.0	B
Vest4		0.076
MutPred		0.23		Gain of MoRF binding (P = 0.0106)
MVP		0.040
MPC		0.40
ClinPred		0.023	T
GERP RS		2.4
Varity_R		0.043
gMVP		0.040

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: rs1465184634; hg19: chr17-5124612;