1-3463528-C-A

Variant names:

• chr1-3463528-C-A
• NM_014448.4:c.444C>A

Variant summary

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

The NM_014448.4(ARHGEF16):​c.444C>A​(p.Asn148Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000227 in 1,320,796 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. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000023 (0 hom.)
• Consequence: ARHGEF16 NM_014448.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00500

Genes affected

ARHGEF16 (HGNC:15515): (Rho guanine nucleotide exchange factor 16) Although the specific function of this protein is not known yet, it is thought to be involved in protein-protein and protein-lipid interactions. [provided by RefSeq, Jul 2008]

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=0.15771383).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGEF16	NM_014448.4	c.444C>A	p.Asn148Lys	missense_variant	Exon 2 of 15	ENST00000378378.9	NP_055263.2
ARHGEF16	XM_017001049.2	c.495C>A	p.Asn165Lys	missense_variant	Exon 2 of 15		XP_016856538.1
ARHGEF16	XM_017001051.2	c.444C>A	p.Asn148Lys	missense_variant	Exon 2 of 15		XP_016856540.1
ARHGEF16	XM_047418009.1	c.495C>A	p.Asn165Lys	missense_variant	Exon 2 of 8		XP_047273965.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGEF16	ENST00000378378.9	c.444C>A	p.Asn148Lys	missense_variant	Exon 2 of 15	2	NM_014448.4	ENSP00000367629.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000227 AC: 3 AN: 1320796 Hom.: 0 Cov.: 31 AF XY: 0.00000155 AC XY: 1 AN XY: 643100

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000192

Gnomad4 OTH exome AF: 0.0000184

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.067	T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.64
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.068	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.6	M
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.12
Sift	Benign	0.11	T
Sift4G	Benign	0.13	T
Polyphen		0.59	P
Vest4		0.13
MutPred		0.28		Gain of methylation at N148 (P = 0.0162);
MVP		0.45
MPC		0.32
ClinPred		0.71	D
GERP RS		1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.4
Varity_R		0.19
gMVP		0.48

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-3380092;