3-119295140-CTTTTTTTTT-CTTTTTTT

Variant names:

• chr3-119295140-CTT-C
• rs10707359
• NM_020754.4:c.100+147_100+148delTT

Variant summary

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

The NM_020754.4(ARHGAP31):​c.100+147_100+148delTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00111 in 620,370 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAd4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000043 (0 hom., cov: 17)
  • Exomes 𝑓: 0.0014 (0 hom.)
• Consequence: ARHGAP31 NM_020754.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0770
• Publications: 0 publications found

Genes affected

ARHGAP31 (HGNC:29216): (Rho GTPase activating protein 31) This gene encodes a GTPase-activating protein (GAP). A variety of cellular processes are regulated by Rho GTPases which cycle between an inactive form bound to GDP and an active form bound to GTP. This cycling between inactive and active forms is regulated by guanine nucleotide exchange factors and GAPs. The encoded protein is a GAP shown to regulate two GTPases involved in protein trafficking and cell growth. [provided by RefSeq, Jul 2008]

ARHGAP31 Gene-Disease associations (from GenCC):

• Adams-Oliver syndrome 1

  Inheritance: AD Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• Adams-Oliver syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP31	NM_020754.4	c.100+147_100+148delTT		intron_variant	Intron 1 of 11	ENST00000264245.9	NP_065805.2
ARHGAP31	XM_006713714.4	c.100+147_100+148delTT		intron_variant	Intron 1 of 11		XP_006713777.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP31	ENST00000264245.9	c.100+137_100+138delTT		intron_variant	Intron 1 of 11	1	NM_020754.4	ENSP00000264245.4

Frequencies

GnomAD3 genomes AF: 0.0000358 AC: 5 AN: 139828 Hom.: 0 Cov.: 17

Gnomad AFR AF: 0.0000775

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: 0.000121

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000156

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00143 AC: 685 AN: 480472 Hom.: 0 AF XY: 0.00142 AC XY: 364 AN XY: 256858

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00695 AC: 79 AN: 11366

American (AMR) AF: 0.00107 AC: 21 AN: 19610

Ashkenazi Jewish (ASJ) AF: 0.000815 AC: 12 AN: 14722

East Asian (EAS) AF: 0.000556 AC: 14 AN: 25196

South Asian (SAS) AF: 0.00193 AC: 89 AN: 46098

European-Finnish (FIN) AF: 0.00104 AC: 30 AN: 28934

Middle Eastern (MID) AF: 0.00243 AC: 7 AN: 2884

European-Non Finnish (NFE) AF: 0.00127 AC: 390 AN: 306504

Other (OTH) AF: 0.00171 AC: 43 AN: 25158

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000429 AC: 6 AN: 139898 Hom.: 0 Cov.: 17 AF XY: 0.0000444 AC XY: 3 AN XY: 67594

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000103 AC: 4 AN: 38786

American (AMR) AF: 0.00 AC: 0 AN: 13514

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3246

East Asian (EAS) AF: 0.00 AC: 0 AN: 4668

South Asian (SAS) AF: 0.00 AC: 0 AN: 4320

European-Finnish (FIN) AF: 0.000121 AC: 1 AN: 8238

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 280

European-Non Finnish (NFE) AF: 0.0000156 AC: 1 AN: 64056

Other (OTH) AF: 0.00 AC: 0 AN: 1928

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.004937), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 50

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.077

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs10707359; hg19: chr3-119013987;