10-106579195-A-T

Variant names:

• chr10-106579195-A-T
• NM_052918.5:c.3371+174T>A

Variant summary

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

The NM_001387556.1(SORCS1):​c.3428T>A​(p.Met1143Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,844 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: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SORCS1 NM_001387556.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.16

Genes affected

SORCS1 (HGNC:16697): (sortilin related VPS10 domain containing receptor 1) This gene encodes one family member of vacuolar protein sorting 10 (VPS10) domain-containing receptor proteins. The VPS10 domain name comes from the yeast carboxypeptidase Y sorting receptor Vps10 protein. Members of this gene family are large with many exons but the CDS lengths are usually less than 3700 nt. Very large introns typically separate the exons encoding the VPS10 domain; the remaining exons are separated by much smaller-sized introns. These genes are strongly expressed in the central nervous system. Two of the five family members (sortilin and sortilin-related receptor) are synthesized as preproproteins; it is not yet known if this encoded protein is also a preproprotein. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

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 rank	MANE	Protein	UniProt
SORCS1	NM_052918.5	c.3371+174T>A		intron_variant	Intron 25 of 25	ENST00000263054.11	NP_443150.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SORCS1	ENST00000263054.11	c.3371+174T>A		intron_variant	Intron 25 of 25	1	NM_052918.5	ENSP00000263054.5
SORCS1	ENST00000369698.6	c.2159T>A	p.Met720Lys	missense_variant	Exon 18 of 19	5		ENSP00000358712.2
SORCS1	ENST00000452214.5	c.470T>A	p.Met157Lys	missense_variant	Exon 5 of 6	3		ENSP00000407769.1
SORCS1	ENST00000473866.1	n.316T>A		non_coding_transcript_exon_variant	Exon 4 of 4	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461844 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727224

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: 8.99e-7

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.056	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	20
DANN	Uncertain	0.99
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.87	D;T;T
M_CAP	Benign	0.031	D
MetaRNN	Uncertain	0.43	T;T;T
MetaSVM	Benign	-0.51	T
PrimateAI	Uncertain	0.52	T
PROVEAN	Pathogenic	-4.9	.;D;.
REVEL	Benign	0.22
Sift	Uncertain	0.0020	.;D;.
Sift4G	Uncertain	0.0020	D;D;D
Vest4		0.70
MVP		0.10
MPC		0.61
ClinPred		0.92	D
GERP RS		5.8

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr10-108338953;