X-9846244-T-C

Variant names:

• chrX-9846244-T-C
• rs2405943
• NM_001649.4:c.166-27408T>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001649.4(SHROOM2):​c.166-27408T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.78 (24085 hom., 23127 hem., cov: 21)
  • Failed GnomAD Quality Control
• Consequence: SHROOM2 NM_001649.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.57
• Publications: 4 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.07).

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.166-27408T>C		intron	N/A	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.166-27408T>C		intron	N/A	ENSP00000370299.3	Q13796
	ENSG00000310579	ENST00000850985.1		c.166-27408T>C		intron	N/A	ENSP00000521067.1

Frequencies

GnomAD3 genomes AF: 0.782 AC: 84037 AN: 107461 Hom.: 24077 Cov.: 21

Gnomad AFR AF: 0.744

Gnomad AMI AF: 0.780

Gnomad AMR AF: 0.881

Gnomad ASJ AF: 0.737

Gnomad EAS AF: 0.917

Gnomad SAS AF: 0.462

Gnomad FIN AF: 0.759

Gnomad MID AF: 0.749

Gnomad NFE AF: 0.795

Gnomad OTH AF: 0.801

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.782 AC: 84073 AN: 107510 Hom.: 24085 Cov.: 21 AF XY: 0.773 AC XY: 23127 AN XY: 29936

African (AFR) AF: 0.744 AC: 21849 AN: 29377

American (AMR) AF: 0.881 AC: 8723 AN: 9903

Ashkenazi Jewish (ASJ) AF: 0.737 AC: 1915 AN: 2600

East Asian (EAS) AF: 0.917 AC: 3109 AN: 3391

South Asian (SAS) AF: 0.462 AC: 1114 AN: 2413

European-Finnish (FIN) AF: 0.759 AC: 4099 AN: 5400

Middle Eastern (MID) AF: 0.748 AC: 154 AN: 206

European-Non Finnish (NFE) AF: 0.795 AC: 41430 AN: 52109

Other (OTH) AF: 0.803 AC: 1163 AN: 1448

Alfa AF: 0.619 Hom.: 2284

Bravo AF: 0.798

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.40
DANN	Benign	0.11
PhyloP100		-3.6
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: rs2405943; hg19: chrX-9814284;