rs10542660

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001353921.2(ARHGEF9):c.*158_*181delCACACACACACACACACACACACA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000937 in 213,484 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 12)

Exomes 𝑓: 0.0000094 ( 0 hom. 2 hem. )

Consequence

ARHGEF9
NM_001353921.2 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.56

Publications

0 publications found

Variant links:

Genes affected

ARHGEF9 (HGNC:14561): (Cdc42 guanine nucleotide exchange factor 9) The protein encoded by this gene is a Rho-like GTPase that switches between the active (GTP-bound) state and inactive (GDP-bound) state to regulate CDC42 and other genes. This brain-specific protein also acts as an adaptor protein for the recruitment of gephyrin and together these proteins facilitate receceptor recruitement in GABAnergic and glycinergic synapses. Defects in this gene are the cause of startle disease with epilepsy (STHEE), also known as hyperekplexia with epilepsy, as well as several other types of cognitive disability. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2017]

ARHGEF9 Gene-Disease associations (from GenCC):

developmental and epileptic encephalopathy, 8
Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, G2P
X-linked complex neurodevelopmental disorder
Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen

ARHGEF9 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High Hemizygotes in GnomAdExome4 at 2 XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001353921.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ARHGEF9	NM_001353921.2	MANE Select	c.158_181delCACACACACACACACACACACACA	3_prime_UTR	Exon 10 of 10	NP_001340850.1	A0A5F9ZHY9
ARHGEF9	NM_001353923.1		c.158_181delCACACACACACACACACACACACA	3_prime_UTR	Exon 10 of 10	NP_001340852.1	A0A1B0GWI5
ARHGEF9	NM_001369030.1		c.158_181delCACACACACACACACACACACACA	3_prime_UTR	Exon 11 of 11	NP_001355959.1	O43307-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ARHGEF9	ENST00000671741.2	MANE Select	c.158_181delCACACACACACACACACACACACA	3_prime_UTR	Exon 10 of 10	ENSP00000500715.1	A0A5F9ZHY9
ARHGEF9	ENST00000253401.10	TSL:1	c.158_181delCACACACACACACACACACACACA	3_prime_UTR	Exon 10 of 10	ENSP00000253401.6	O43307-1
ARHGEF9	ENST00000374878.5	TSL:1	c.1375-2462_1375-2439delCACACACACACACACACACACACA	intron	N/A	ENSP00000364012.2	B1AMR4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000937

AC:

AN:

213484

Hom.:

AF XY:

0.0000314

AC XY:

AN XY:

63654

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

6675

American (AMR)

AF:

0.00

AC:

AN:

8273

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

6829

East Asian (EAS)

AF:

0.00

AC:

AN:

17304

South Asian (SAS)

AF:

0.000132

AC:

AN:

7596

European-Finnish (FIN)

AF:

0.00

AC:

AN:

14833

Middle Eastern (MID)

AF:

0.00

AC:

AN:

917

European-Non Finnish (NFE)

AF:

0.00000726

AC:

AN:

137718

Other (OTH)

AF:

0.00

AC:

AN:

13339

Age Distribution

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

3.6

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over