NM_173519.3:c.977+159C>A

Variant names:

• chr8-61458701-C-A
• rs2291607
• NM_173519.3:c.977+159C>A

Variant summary

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

The NM_173519.3(CLVS1):​c.977+159C>A variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CLVS1 NM_173519.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.192
• Publications: 3 publications found

Genes affected

CLVS1 (HGNC:23139): (clavesin 1) Enables phosphatidylinositol-3,5-bisphosphate binding activity. Predicted to be involved in lysosome organization. Located in endosome. [provided by Alliance of Genome Resources, Apr 2022]

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 (BayesDel_noAF=-0.46).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173519.3. 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
	CLVS1	NM_173519.3	MANE Select	c.977+159C>A		intron	N/A	NP_775790.1	Q8IUQ0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLVS1	ENST00000325897.5	TSL:1 MANE Select	c.977+159C>A		intron	N/A	ENSP00000325506.4	Q8IUQ0-1
	CLVS1	ENST00000518592.5	TSL:1	c.140+159C>A		intron	N/A	ENSP00000429869.1	G3V122
	CLVS1	ENST00000519846.5	TSL:5	c.977+159C>A		intron	N/A	ENSP00000428402.1	Q8IUQ0-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 424156 Hom.: 0 Cov.: 5 AF XY: 0.00 AC XY: 0 AN XY: 221290

African (AFR) AF: 0.00 AC: 0 AN: 11884

American (AMR) AF: 0.00 AC: 0 AN: 12958

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12952

East Asian (EAS) AF: 0.00 AC: 0 AN: 28946

South Asian (SAS) AF: 0.00 AC: 0 AN: 35352

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30648

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3046

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 263942

Other (OTH) AF: 0.00 AC: 0 AN: 24428

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 132451

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	11
DANN	Benign	0.60
PhyloP100		0.19

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: rs2291607; hg19: chr8-62371260;