rs1440153497

Variant names:

• chr17-12974210-C-G
• rs1440153497
• NM_014859.6:c.1663C>G

Your query was ambiguous. Multiple possible variants found:

• chr17-12974210-C-G
• chr17-12974210-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014859.6(ARHGAP44):​c.1663C>G​(p.Pro555Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,172 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: ARHGAP44 NM_014859.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.412

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06860459).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP44	NM_014859.6	c.1663C>G	p.Pro555Ala	missense_variant	Exon 18 of 21	ENST00000379672.10	NP_055674.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP44	ENST00000379672.10	c.1663C>G	p.Pro555Ala	missense_variant	Exon 18 of 21	1	NM_014859.6	ENSP00000368994.5

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152172 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152172 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74324

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.053
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	13
DANN	Benign	0.85
DEOGEN2	Benign	0.023	T;.;T;.
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.70	T;T;T;T
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.069	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.97	L;.;.;.
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.75	N;N;.;.
REVEL	Benign	0.077
Sift	Benign	0.54	T;T;.;.
Sift4G	Benign	0.60	T;T;T;T
Polyphen		0.0080	B;.;.;.
Vest4		0.12
MutPred		0.23		Loss of glycosylation at P555 (P = 0.0309);.;Loss of glycosylation at P555 (P = 0.0309);.;
MVP		0.068
MPC		0.67
ClinPred		0.077	T
GERP RS		5.0
Varity_R		0.055
gMVP		0.21

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

Publications

LitVar

Other links and lift over

dbSNP: rs1440153497; hg19: chr17-12877527;