rs61736492

Variant names:

• chr11-106939762-T-A
• NM_000855.3:c.904A>T

Your query was ambiguous. Multiple possible variants found:

• chr11-106939762-T-A
• chr11-106939762-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000855.3(GUCY1A2):​c.904A>T​(p.Met302Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,710 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M302V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: GUCY1A2 NM_000855.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.03

Genes affected

GUCY1A2 (HGNC:4684): (guanylate cyclase 1 soluble subunit alpha 2) Soluble guanylate cyclases are heterodimeric proteins that catalyze the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. The protein encoded by this gene is an alpha subunit of this complex and it interacts with a beta subunit to form the guanylate cyclase enzyme, which is activated by nitric oxide. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1352211).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GUCY1A2	NM_000855.3	c.904A>T	p.Met302Leu	missense_variant	Exon 4 of 8	ENST00000526355.7	NP_000846.1
GUCY1A2	NM_001256424.2	c.904A>T	p.Met302Leu	missense_variant	Exon 4 of 9		NP_001243353.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GUCY1A2	ENST00000526355.7	c.904A>T	p.Met302Leu	missense_variant	Exon 4 of 8	1	NM_000855.3	ENSP00000431245.2
GUCY1A2	ENST00000282249.6	c.904A>T	p.Met302Leu	missense_variant	Exon 4 of 9	1		ENSP00000282249.2
GUCY1A2	ENST00000347596.2	c.904A>T	p.Met302Leu	missense_variant	Exon 4 of 9	1		ENSP00000344874.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461710 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727142

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: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	0.46
DANN	Benign	0.37
DEOGEN2	Benign	0.068	T;.;.
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.70
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.45	T;T;T
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.14	T;T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	0.34	N;N;N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.24	N;N;N
REVEL	Benign	0.086
Sift	Benign	0.32	T;T;T
Sift4G	Benign	0.32	T;T;T
Polyphen		0.0	B;B;.
Vest4		0.15
MutPred		0.32		Gain of methylation at K303 (P = 0.0446);Gain of methylation at K303 (P = 0.0446);Gain of methylation at K303 (P = 0.0446);
MVP		0.65
MPC		0.48
ClinPred		0.13	T
GERP RS		1.9
Varity_R		0.097
gMVP		0.17

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-106810488;