17-12949142-A-T

Variant names:

• chr17-12949142-A-T
• rs2072254
• NM_014859.6:c.864A>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_014859.6(ARHGAP44):​c.864A>T​(p.Gly288Gly) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 151,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ARHGAP44 NM_014859.6 splice_region, synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05
• Publications: 15 publications found

Genes affected

ARHGAP44 (HGNC:29096): (Rho GTPase activating protein 44) Enables phospholipid binding activity. Predicted to be involved in several processes, including modification of dendritic spine; negative regulation of Rac protein signal transduction; and regulation of plasma membrane bounded cell projection organization. Located in leading edge membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP7: Synonymous conserved (PhyloP=-1.05 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014859.6. 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
	ARHGAP44	NM_014859.6	MANE Select	c.864A>T	p.Gly288Gly	splice_region synonymous	Exon 11 of 21	NP_055674.4
	ARHGAP44	NM_001321166.2		c.864A>T	p.Gly288Gly	splice_region synonymous	Exon 11 of 20	NP_001308095.1
	ARHGAP44	NM_001321167.2		c.864A>T	p.Gly288Gly	splice_region synonymous	Exon 11 of 22	NP_001308096.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP44	ENST00000379672.10	TSL:1 MANE Select	c.864A>T	p.Gly288Gly	splice_region synonymous	Exon 11 of 21	ENSP00000368994.5
	ARHGAP44	ENST00000340825.7	TSL:1	c.864A>T	p.Gly288Gly	splice_region synonymous	Exon 11 of 20	ENSP00000342566.3
	ARHGAP44	ENST00000262444.13	TSL:1	c.864A>T	p.Gly288Gly	splice_region synonymous	Exon 11 of 22	ENSP00000262444.9

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151764 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1412852 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 698138

African (AFR) AF: 0.00 AC: 0 AN: 32174

American (AMR) AF: 0.00 AC: 0 AN: 37226

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25290

East Asian (EAS) AF: 0.00 AC: 0 AN: 36654

South Asian (SAS) AF: 0.00 AC: 0 AN: 79924

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50132

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5720

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1087000

Other (OTH) AF: 0.00 AC: 0 AN: 58732

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151882 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74230

African (AFR) AF: 0.00 AC: 0 AN: 41402

American (AMR) AF: 0.00 AC: 0 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000195 AC: 1 AN: 5138

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10548

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67952

Other (OTH) AF: 0.00 AC: 0 AN: 2098

Alfa AF: 0.00 Hom.: 425

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	8.6
DANN	Benign	0.80
PhyloP100		-1.1

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: rs2072254; hg19: chr17-12852459;