chr22-24546909-C-T

Variant names:

• chr22-24546909-C-T
• NM_001284254.2:c.386+5G>A

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001284254.2(GUCD1):​c.386+5G>A variant causes a splice region, intron change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GUCD1 NM_001284254.2 splice_region, intron
• Scores: Splicing: ADA: 1.000
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.45
• Publications: 0 publications found

Genes affected

GUCD1 (HGNC:14237): (guanylyl cyclase domain containing 1)

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF, max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001284254.2. 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
	GUCD1	NM_001284254.2	MANE Select	c.386+5G>A		splice_region intron	N/A	NP_001271183.1	Q96NT3-2
	GUCD1	NM_001284251.2		c.554+5G>A		splice_region intron	N/A	NP_001271180.1	A0A087WVD9
	GUCD1	NM_001284252.2		c.554+5G>A		splice_region intron	N/A	NP_001271181.1	Q96NT3-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GUCD1	ENST00000435822.6	TSL:1 MANE Select	c.386+5G>A		splice_region intron	N/A	ENSP00000405985.1	Q96NT3-2
	GUCD1	ENST00000621833.4	TSL:1	c.554+5G>A		splice_region intron	N/A	ENSP00000479370.1	A0A087WVD9
	GUCD1	ENST00000404664.7	TSL:2	c.554+5G>A		splice_region intron	N/A	ENSP00000384121.3	Q96NT3-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.15
CADD	Pathogenic	35
DANN	Benign	0.97
PhyloP100		6.4

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.99
SpliceAI score (max)		0.54		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.54		Position offset: 22
DS_DL_spliceai		0.27		Position offset: 5

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr22-24942877;