X-9891058-A-G

Variant names:

• chrX-9891058-A-G
• rs6640543
• NM_001649.4:c.399A>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6 BP7

The NM_001649.4(SHROOM2):​c.399A>G​(p.Pro133Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Synonymous variant affecting the same amino acid position (i.e. P133P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.87 (29542 hom., 29245 hem., cov: 23)
  • Exomes 𝑓: 0.94 (321587 hom. 336402 hem.)
  • Failed GnomAD Quality Control
• Consequence: SHROOM2 NM_001649.4 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.374
• Publications: 12 publications found

Genes affected

SHROOM2 (HGNC:630): (shroom family member 2) This gene represents the human homolog of Xenopus laevis apical protein (APX) gene, which is implicated in amiloride-sensitive sodium channel activity. It is expressed in endothelial cells and facilitates the formation of a contractile network within endothelial cells. Depletion of this gene results in an increase in endothelial sprouting, migration, and angiogenesis. This gene is highly expressed in the retina, and is a strong candidate for ocular albinism type 1 syndrome. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Mar 2016]

ENSG00000310579 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant X-9891058-A-G is Benign according to our data. Variant chrX-9891058-A-G is described in ClinVar as Benign. ClinVar VariationId is 3059401.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=0.374 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001649.4. 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
	SHROOM2	NM_001649.4	MANE Select	c.399A>G	p.Pro133Pro	synonymous	Exon 3 of 10	NP_001640.1	Q13796

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHROOM2	ENST00000380913.8	TSL:1 MANE Select	c.399A>G	p.Pro133Pro	synonymous	Exon 3 of 10	ENSP00000370299.3	Q13796
	ENSG00000310579	ENST00000850985.1		c.399A>G	p.Pro133Pro	synonymous	Exon 3 of 10	ENSP00000521067.1
	ENSG00000295228	ENST00000728736.1		n.133+6T>C		splice_region intron	N/A

Frequencies

GnomAD3 genomes AF: 0.865 AC: 96295 AN: 111308 Hom.: 29549 Cov.: 23

Gnomad AFR AF: 0.665

Gnomad AMI AF: 0.987

Gnomad AMR AF: 0.931

Gnomad ASJ AF: 0.930

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.958

Gnomad FIN AF: 0.943

Gnomad MID AF: 0.903

Gnomad NFE AF: 0.939

Gnomad OTH AF: 0.879

GnomAD2 exomes AF: 0.929 AC: 149807 AN: 161308 AF XY: 0.937

Gnomad AFR exome AF: 0.665

Gnomad AMR exome AF: 0.957

Gnomad ASJ exome AF: 0.920

Gnomad EAS exome AF: 0.996

Gnomad FIN exome AF: 0.941

Gnomad NFE exome AF: 0.940

Gnomad OTH exome AF: 0.929

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.937 AC: 1022028 AN: 1091251 Hom.: 321587 Cov.: 47 AF XY: 0.939 AC XY: 336402 AN XY: 358305

African (AFR) AF: 0.662 AC: 17386 AN: 26254

American (AMR) AF: 0.955 AC: 32845 AN: 34393

Ashkenazi Jewish (ASJ) AF: 0.924 AC: 17753 AN: 19218

East Asian (EAS) AF: 0.993 AC: 29707 AN: 29924

South Asian (SAS) AF: 0.959 AC: 50597 AN: 52768

European-Finnish (FIN) AF: 0.940 AC: 37538 AN: 39920

Middle Eastern (MID) AF: 0.884 AC: 3643 AN: 4120

European-Non Finnish (NFE) AF: 0.942 AC: 790305 AN: 838867

Other (OTH) AF: 0.923 AC: 42254 AN: 45787

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.865 AC: 96337 AN: 111359 Hom.: 29542 Cov.: 23 AF XY: 0.872 AC XY: 29245 AN XY: 33543

African (AFR) AF: 0.666 AC: 20347 AN: 30563

American (AMR) AF: 0.932 AC: 9854 AN: 10578

Ashkenazi Jewish (ASJ) AF: 0.930 AC: 2463 AN: 2649

East Asian (EAS) AF: 0.997 AC: 3511 AN: 3523

South Asian (SAS) AF: 0.957 AC: 2545 AN: 2658

European-Finnish (FIN) AF: 0.943 AC: 5621 AN: 5960

Middle Eastern (MID) AF: 0.898 AC: 194 AN: 216

European-Non Finnish (NFE) AF: 0.939 AC: 49799 AN: 53019

Other (OTH) AF: 0.880 AC: 1329 AN: 1510

Alfa AF: 0.905 Hom.: 11925

Bravo AF: 0.856

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	SHROOM2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.85
DANN	Benign	0.29
PhyloP100		0.37
Mutation Taster		=100/0	polymorphism (auto)

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: rs6640543; hg19: chrX-9859098; COSMIC: COSV66609335;