22-24554955-C-T

Variant names:

• chr22-24554955-C-T
• NM_001284254.2:c.37G>A

Variant summary

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

The NM_001284254.2(GUCD1):​c.37G>A​(p.Glu13Lys) 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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GUCD1 NM_001284254.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.96
• Publications: 0 publications found

Genes affected

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

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 (MetaRNN=0.15192011).

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.37G>A	p.Glu13Lys	missense	Exon 1 of 6	NP_001271183.1	Q96NT3-2
	GUCD1	NM_031444.4		c.37G>A	p.Glu13Lys	missense	Exon 1 of 6	NP_113632.2	Q96NT3-1
	GUCD1	NM_001284255.2		c.37G>A	p.Glu13Lys	missense	Exon 1 of 6	NP_001271184.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GUCD1	ENST00000435822.6	TSL:1 MANE Select	c.37G>A	p.Glu13Lys	missense	Exon 1 of 6	ENSP00000405985.1	Q96NT3-2
	GUCD1	ENST00000621833.4	TSL:1	c.211+660G>A		intron	N/A	ENSP00000479370.1	A0A087WVD9
	GUCD1	ENST00000407471.7	TSL:5	c.37G>A	p.Glu13Lys	missense	Exon 1 of 6	ENSP00000386076.3	Q96NT3-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1417802 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 706186

African (AFR) AF: 0.00 AC: 0 AN: 29014

American (AMR) AF: 0.00 AC: 0 AN: 38408

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24612

East Asian (EAS) AF: 0.00 AC: 0 AN: 34328

South Asian (SAS) AF: 0.00 AC: 0 AN: 83130

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51342

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5602

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1093136

Other (OTH) AF: 0.00 AC: 0 AN: 58230

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.026	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.024	T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.13
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.49	N
PhyloP100		2.0
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-0.35	N
REVEL	Benign	0.066
Sift	Benign	0.28	T
Sift4G	Benign	0.65	T
Polyphen		0.043	B
Vest4		0.26
MutPred		0.38		Gain of ubiquitination at E13 (P = 0.0018)
MVP		0.58
MPC		0.27
ClinPred		0.39	T
GERP RS		3.6
PromoterAI		-0.0042	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.32
Mutation Taster		=93/7	polymorphism

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

hg19: chr22-24950923;