NM_014629.4:c.38-44_38-33delATCTATCTATCT

Variant names:

• chr8-1857879-GATCTATCTATCT-G
• rs35698984
• NM_014629.4:c.38-44_38-33delATCTATCTATCT

Variant summary

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

The NM_014629.4(ARHGEF10):​c.38-44_38-33delATCTATCTATCT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000579 in 594,360 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.00049 (0 hom., cov: 24)
  • Exomes 𝑓: 0.00060 (0 hom.)
• Consequence: ARHGEF10 NM_014629.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.10
• Publications: 1 publications found

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

KBTBD11-OT1 (HGNC:):

ACMG classification

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

• BS2: High AC in GnomAd4 at 56 Unknown,AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGEF10	NM_014629.4	MANE Select	c.38-44_38-33delATCTATCTATCT		intron	N/A	NP_055444.2	O15013-5
	ARHGEF10	NM_001438091.1		c.38-44_38-33delATCTATCTATCT		intron	N/A	NP_001425020.1
	ARHGEF10	NM_001308153.3		c.38-44_38-33delATCTATCTATCT		intron	N/A	NP_001295082.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGEF10	ENST00000349830.8	TSL:1 MANE Select	c.38-80_38-69delATCTATCTATCT		intron	N/A	ENSP00000340297.3	O15013-5
	ARHGEF10	ENST00000518288.5	TSL:1	c.110-80_110-69delATCTATCTATCT		intron	N/A	ENSP00000431012.1	O15013-6
	ARHGEF10	ENST00000520359.5	TSL:1	c.38-80_38-69delATCTATCTATCT		intron	N/A	ENSP00000427909.1	O15013-7

Frequencies

GnomAD3 genomes AF: 0.000493 AC: 56 AN: 113632 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.000884

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000619

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000552

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000403

Gnomad OTH AF: 0.000644

GnomAD4 exome AF: 0.000599 AC: 288 AN: 480656 Hom.: 0 AF XY: 0.000667 AC XY: 170 AN XY: 255060

African (AFR) AF: 0.00105 AC: 12 AN: 11422

American (AMR) AF: 0.000263 AC: 6 AN: 22832

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13808

East Asian (EAS) AF: 0.000145 AC: 4 AN: 27590

South Asian (SAS) AF: 0.00136 AC: 62 AN: 45536

European-Finnish (FIN) AF: 0.000117 AC: 4 AN: 34238

Middle Eastern (MID) AF: 0.00130 AC: 3 AN: 2300

European-Non Finnish (NFE) AF: 0.000618 AC: 184 AN: 297942

Other (OTH) AF: 0.000520 AC: 13 AN: 24988

GnomAD4 genome AF: 0.000493 AC: 56 AN: 113704 Hom.: 0 Cov.: 24 AF XY: 0.000472 AC XY: 26 AN XY: 55142

African (AFR) AF: 0.000881 AC: 24 AN: 27228

American (AMR) AF: 0.000618 AC: 7 AN: 11318

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2696

East Asian (EAS) AF: 0.00 AC: 0 AN: 4316

South Asian (SAS) AF: 0.000551 AC: 2 AN: 3630

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7438

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 210

European-Non Finnish (NFE) AF: 0.000403 AC: 22 AN: 54642

Other (OTH) AF: 0.000639 AC: 1 AN: 1564

Alfa AF: 0.00 Hom.: 20

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs35698984; hg19: chr8-1806045;