17-5221317-T-G

Variant names:

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

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>C​(p.His60Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H60R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SCIMP NM_207103.3 missense
• Clinical Significance: Not reported in ClinVar
• 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=0.06735203).

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>C	p.His60Pro	missense	Exon 3 of 5	NP_996986.1	Q6UWF3-1
	SCIMP	NM_001271842.1		c.158A>C	p.His53Pro	missense	Exon 3 of 5	NP_001258771.1	Q6UWF3-3
	SCIMP	NM_001319190.2		c.158A>C	p.His53Pro	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>C	p.His60Pro	missense	Exon 3 of 5	ENSP00000461269.1	Q6UWF3-1
	SCIMP	ENST00000399600.8	TSL:1	c.158A>C	p.His53Pro	missense	Exon 3 of 5	ENSP00000382509.4	Q6UWF3-3
	ZNF594-DT	ENST00000571689.1	TSL:1	n.514-2000T>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	14
DANN	Benign	0.72
DEOGEN2	Benign	0.20	T
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.048	N
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.067	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.39
PrimateAI	Benign	0.28	T
REVEL	Benign	0.028
Sift4G	Benign	0.089	T
Polyphen		0.0020	B
Vest4		0.14
MutPred		0.25		Gain of glycosylation at H60 (P = 0.0609)
MVP		0.22
MPC		0.50
ClinPred		0.069	T
GERP RS		2.4
Varity_R		0.19
gMVP		0.13

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;