Genetic Variant ARHGEF10:c.38-82_38-81insAATC (chr8-1857875-G-GATCA) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_014629.4(ARHGEF10):c.38-82_38-81insAATC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000218 in 918,448 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000093 ( 0 hom., cov: 21)

Exomes 𝑓: 0.0000012 ( 0 hom. )

Consequence

ARHGEF10
NM_014629.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.310

Publications

1 publications found

Variant links:

Genes affected

ARHGEF10 (HGNC:14103): (Rho guanine nucleotide exchange factor 10) This gene encodes a Rho guanine nucleotide exchange factor (GEF). Rho GEFs regulate the activity of small Rho GTPases by stimulating the exchange of guanine diphosphate (GDP) for guanine triphosphate (GTP) and may play a role in neural morphogenesis. Mutations in this gene are associated with slowed nerve conduction velocity (SNCV). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]

ARHGEF10 Gene-Disease associations (from GenCC):

autosomal dominant slowed nerve conduction velocity
Inheritance: Unknown, AD Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet
hereditary peripheral neuropathy
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
peripheral neuropathy
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ARHGEF10 links:

KBTBD11-OT1 (HGNC:):

KBTBD11-OT1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014629.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ARHGEF10	NM_014629.4	MANE Select	c.38-82_38-81insAATC	intron	N/A	NP_055444.2	O15013-5
ARHGEF10	NM_001438091.1		c.38-82_38-81insAATC	intron	N/A	NP_001425020.1
ARHGEF10	NM_001308153.3		c.38-82_38-81insAATC	intron	N/A	NP_001295082.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ARHGEF10	ENST00000349830.8	TSL:1 MANE Select	c.38-85_38-84insATCA	intron	N/A	ENSP00000340297.3	O15013-5
ARHGEF10	ENST00000518288.5	TSL:1	c.110-85_110-84insATCA	intron	N/A	ENSP00000431012.1	O15013-6
ARHGEF10	ENST00000520359.5	TSL:1	c.38-85_38-84insATCA	intron	N/A	ENSP00000427909.1	O15013-7

Frequencies

GnomAD3 genomes

AF:

0.00000932

AC:

AN:

107330

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000325

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000123

AC:

AN:

811118

Hom.:

AF XY:

0.00

AC XY:

AN XY:

418256

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

20208

American (AMR)

AF:

0.00

AC:

AN:

32524

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20104

East Asian (EAS)

AF:

0.0000308

AC:

AN:

32450

South Asian (SAS)

AF:

0.00

AC:

AN:

61300

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45518

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3816

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

557016

Other (OTH)

AF:

0.00

AC:

AN:

38182

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000932

AC:

AN:

107330

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

51836

show subpopulations

African (AFR)

AF:

0.0000325

AC:

AN:

30726

American (AMR)

AF:

0.00

AC:

AN:

10218

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2290

East Asian (EAS)

AF:

0.00

AC:

AN:

3498

South Asian (SAS)

AF:

0.00

AC:

AN:

3402

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6132

Middle Eastern (MID)

AF:

0.00

AC:

AN:

222

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

48762

Other (OTH)

AF:

0.00

AC:

AN:

1474

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.31

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