8-1957657-A-T

Variant names:

• chr8-1957657-A-T
• rs6991392
• NM_014629.4:c.*394A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001438091.1(ARHGEF10):​c.*394A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ARHGEF10 NM_001438091.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21
• Publications: 12 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001438091.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGEF10	NM_014629.4	MANE Select	c.*394A>T		3_prime_UTR	Exon 29 of 29	NP_055444.2
	ARHGEF10	NM_001438091.1		c.*394A>T		3_prime_UTR	Exon 29 of 29	NP_001425020.1
	ARHGEF10	NM_001308153.3		c.*394A>T		3_prime_UTR	Exon 30 of 30	NP_001295082.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGEF10	ENST00000349830.8	TSL:1 MANE Select	c.*394A>T		3_prime_UTR	Exon 29 of 29	ENSP00000340297.3
	ARHGEF10	ENST00000518288.5	TSL:1	c.*394A>T		3_prime_UTR	Exon 30 of 30	ENSP00000431012.1
	ARHGEF10	ENST00000520359.5	TSL:1	c.*394A>T		3_prime_UTR	Exon 28 of 28	ENSP00000427909.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 46074 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 23654

African (AFR) AF: 0.00 AC: 0 AN: 1218

American (AMR) AF: 0.00 AC: 0 AN: 3154

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1388

East Asian (EAS) AF: 0.00 AC: 0 AN: 2152

South Asian (SAS) AF: 0.00 AC: 0 AN: 4096

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1944

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 212

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 29238

Other (OTH) AF: 0.00 AC: 0 AN: 2672

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.27
DANN	Benign	0.48
PhyloP100		-1.2

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: rs6991392; hg19: chr8-1905823;