chr17-5223377-A-G

Position:

• chr17-5223377-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_207103.3(SCIMP):​c.101T>C​(p.Leu34Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,466 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • 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: 4.02

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:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCIMP	NM_207103.3	c.101T>C	p.Leu34Pro	missense_variant	2/5	ENST00000574081.6	NP_996986.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCIMP	ENST00000574081.6	c.101T>C	p.Leu34Pro	missense_variant	2/5	1	NM_207103.3	ENSP00000461269.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461466 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727082

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

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

Dec 10, 2024

The c.101T>C (p.L34P) alteration is located in exon 2 (coding exon 2) of the SCIMP gene. This alteration results from a T to C substitution at nucleotide position 101, causing the leucine (L) at amino acid position 34 to be replaced by a proline (P). 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	0.91
BayesDel_addAF	Pathogenic	0.38	D
BayesDel_noAF	Pathogenic	0.31
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T;.;.;T
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Benign	0.34	N
LIST_S2	Benign	0.66	T;T;T;T
M_CAP	Benign	0.026	D
MetaRNN	Uncertain	0.69	D;D;D;D
MetaSVM	Uncertain	-0.27	T
MutationAssessor	Uncertain	2.0	M;M;M;.
PrimateAI	Uncertain	0.50	T
PROVEAN	Pathogenic	-6.4	.;D;.;.
REVEL	Uncertain	0.30
Sift	Pathogenic	0.0	.;D;.;.
Sift4G	Uncertain	0.0040	D;D;D;D
Polyphen		1.0	D;.;D;.
Vest4		0.72
MutPred		0.42		Loss of stability (P = 0.0063);Loss of stability (P = 0.0063);Loss of stability (P = 0.0063);Loss of stability (P = 0.0063);
MVP		0.39
MPC		1.4
ClinPred		0.98	D
GERP RS		5.5
Varity_R		0.94
gMVP		0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr17-5126672;