rs12123693

Variant names:

• chr1-170016183-C-T
• rs12123693
• NM_014970.4:c.1183+279G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014970.4(KIFAP3):​c.1183+279G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 151,802 control chromosomes in the GnomAD database, including 2,227 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.17 (2227 hom., cov: 32)
• Consequence: KIFAP3 NM_014970.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.479
• Publications: 3 publications found

Genes affected

KIFAP3 (HGNC:17060): (kinesin associated protein 3) The small G protein GDP dissociation stimulator (smg GDS) is a regulator protein having two activities on a group of small G proteins including the Rho and Rap1 family members and Ki-Ras; one is to stimulate their GDP/GTP exchange reactions, and the other is to inhibit their interactions with membranes. The protein encoded by this gene contains 9 'Armadillo' repeats and interacts with the smg GDS protein through these repeats. This protein, which is highly concentrated around the endoplasmic reticulum, is phosphorylated by v-src, and this phosphorylation reduces the affinity of the protein for smg GDS. It is thought that this protein serves as a linker between human chromosome-associated polypeptide (HCAP) and KIF3A/B, a kinesin superfamily protein in the nucleus, and that it plays a role in the interaction of chromosomes with an ATPase motor protein. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2011]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014970.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIFAP3	NM_014970.4	MANE Select	c.1183+279G>A		intron	N/A	NP_055785.2
	KIFAP3	NM_001375830.1		c.1183+279G>A		intron	N/A	NP_001362759.1
	KIFAP3	NM_001375831.1		c.1183+279G>A		intron	N/A	NP_001362760.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIFAP3	ENST00000361580.7	TSL:1 MANE Select	c.1183+279G>A		intron	N/A	ENSP00000354560.2	Q92845-1
	KIFAP3	ENST00000367767.5	TSL:1	c.1051+279G>A		intron	N/A	ENSP00000356741.1	Q92845-2
	KIFAP3	ENST00000490550.2	TSL:5	c.1228+279G>A		intron	N/A	ENSP00000518914.1	A0AAQ5BGI3

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25067 AN: 151684 Hom.: 2226 Cov.: 32

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.206

Gnomad AMR AF: 0.218

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.127

Gnomad SAS AF: 0.204

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.229

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.174

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.165 AC: 25073 AN: 151802 Hom.: 2227 Cov.: 32 AF XY: 0.166 AC XY: 12338 AN XY: 74206

African (AFR) AF: 0.108 AC: 4470 AN: 41404

American (AMR) AF: 0.218 AC: 3326 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.251 AC: 871 AN: 3466

East Asian (EAS) AF: 0.127 AC: 653 AN: 5152

South Asian (SAS) AF: 0.205 AC: 985 AN: 4806

European-Finnish (FIN) AF: 0.178 AC: 1877 AN: 10518

Middle Eastern (MID) AF: 0.223 AC: 65 AN: 292

European-Non Finnish (NFE) AF: 0.181 AC: 12277 AN: 67902

Other (OTH) AF: 0.172 AC: 362 AN: 2106

Alfa AF: 0.178 Hom.: 1334

Bravo AF: 0.164

Asia WGS AF: 0.178 AC: 616 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.7
DANN	Benign	0.58
PhyloP100		-0.48
Mutation Taster		=100/0	polymorphism (auto)

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: rs12123693; hg19: chr1-169985324;