rs141530050

Variant names:

• chr22-24543908-T-C
• rs141530050
• NM_001284254.2:c.562A>G

Your query was ambiguous. Multiple possible variants found:

• chr22-24543908-T-C
• chr22-24543908-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001284254.2(GUCD1):​c.562A>G​(p.Ile188Val) variant causes a missense change. The variant allele was found at a frequency of 0.000206 in 1,613,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00021 (0 hom.)
• Consequence: GUCD1 NM_001284254.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.83
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.16575962).

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.562A>G	p.Ile188Val	missense	Exon 5 of 6	NP_001271183.1	Q96NT3-2
	GUCD1	NM_001284251.2		c.730A>G	p.Ile244Val	missense	Exon 5 of 6	NP_001271180.1	A0A087WVD9
	GUCD1	NM_001284252.2		c.730A>G	p.Ile244Val	missense	Exon 5 of 6	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.562A>G	p.Ile188Val	missense	Exon 5 of 6	ENSP00000405985.1	Q96NT3-2
	GUCD1	ENST00000621833.4	TSL:1	c.730A>G	p.Ile244Val	missense	Exon 5 of 6	ENSP00000479370.1	A0A087WVD9
	GUCD1	ENST00000404664.7	TSL:2	c.730A>G	p.Ile244Val	missense	Exon 5 of 6	ENSP00000384121.3	Q96NT3-3

Frequencies

GnomAD3 genomes AF: 0.000125 AC: 19 AN: 152050 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000757 AC: 19 AN: 251014 AF XY: 0.0000737

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000159

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000214 AC: 313 AN: 1461812 Hom.: 0 Cov.: 32 AF XY: 0.000188 AC XY: 137 AN XY: 727212

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.0000671 AC: 3 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.000270 AC: 300 AN: 1111960

Other (OTH) AF: 0.000166 AC: 10 AN: 60392

GnomAD4 genome AF: 0.000125 AC: 19 AN: 152050 Hom.: 0 Cov.: 32 AF XY: 0.000135 AC XY: 10 AN XY: 74258

African (AFR) AF: 0.0000483 AC: 2 AN: 41396

American (AMR) AF: 0.00 AC: 0 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000250 AC: 17 AN: 67992

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.000245 Hom.: 0

Bravo AF: 0.000113

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.0000659 AC: 8

EpiCase AF: 0.00

EpiControl AF: 0.000296

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	0.085
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	19
DANN	Benign	0.96
DEOGEN2	Benign	0.0074	T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.11
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.16	N
PhyloP100		3.8
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-0.31	N
REVEL	Benign	0.085
Sift	Benign	0.58	T
Sift4G	Benign	0.67	T
Polyphen		0.016	B
Vest4		0.33
MVP		0.67
MPC		0.28
ClinPred		0.11	T
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.055
gMVP		0.38
Mutation Taster		=85/15	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs141530050; hg19: chr22-24939876;