Genetic Variant NM_014629.4:c.38-52_38-33dupATCTATCTATCTATCTATCT (chr8-1857879-G-GATCTATCTATCTATCTATCT) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_014629.4(ARHGEF10):c.38-52_38-33dupATCTATCTATCTATCTATCT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type INS_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: 24)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ARHGEF10
NM_014629.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.397

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 0 ACMG points.

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.38-52_38-33dupATCTATCTATCTATCTATCT	intron	N/A	NP_055444.2	O15013-5
ARHGEF10	NM_001438091.1		c.38-52_38-33dupATCTATCTATCTATCTATCT	intron	N/A	NP_001425020.1
ARHGEF10	NM_001308153.3		c.38-52_38-33dupATCTATCTATCTATCTATCT	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.38-81_38-80insATCTATCTATCTATCTATCT	intron	N/A	ENSP00000340297.3	O15013-5
ARHGEF10	ENST00000518288.5	TSL:1	c.110-81_110-80insATCTATCTATCTATCTATCT	intron	N/A	ENSP00000431012.1	O15013-6
ARHGEF10	ENST00000520359.5	TSL:1	c.38-81_38-80insATCTATCTATCTATCTATCT	intron	N/A	ENSP00000427909.1	O15013-7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000624

AC:

AN:

480670

Hom.:

AF XY:

0.00000392

AC XY:

AN XY:

255066

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

11426

American (AMR)

AF:

0.0000438

AC:

AN:

22832

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13808

East Asian (EAS)

AF:

0.00

AC:

AN:

27590

South Asian (SAS)

AF:

0.0000220

AC:

AN:

45536

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34240

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2300

European-Non Finnish (NFE)

AF:

0.00000336

AC:

AN:

297950

Other (OTH)

AF:

0.00

AC:

AN:

24988

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.408

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.40

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over