rs522444

Variant names:

• chr1-170074763-G-A
• rs522444
• ENST00000490550.2:c.77+10272C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-170074763-G-A
• chr1-170074763-G-C
• chr1-170074763-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000490550.2(KIFAP3):​c.77+10272C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KIFAP3 ENST00000490550.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.243
• Publications: 10 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIFAP3	NM_014970.4	c.-296C>T		upstream_gene_variant		ENST00000361580.7	NP_055785.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIFAP3	ENST00000490550.2	c.77+10272C>T		intron_variant	Intron 1 of 19	5		ENSP00000518914.1
KIFAP3	ENST00000361580.7	c.-296C>T		upstream_gene_variant		1	NM_014970.4	ENSP00000354560.2
KIFAP3	ENST00000367767.5	c.-296C>T		upstream_gene_variant		1		ENSP00000356741.1
KIFAP3	ENST00000538366.5	c.-694C>T		upstream_gene_variant		2		ENSP00000444622.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1098792 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 523312

African (AFR) AF: 0.00 AC: 0 AN: 25106

American (AMR) AF: 0.00 AC: 0 AN: 15128

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13842

East Asian (EAS) AF: 0.00 AC: 0 AN: 24056

South Asian (SAS) AF: 0.00 AC: 0 AN: 41116

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 16740

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2844

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 916900

Other (OTH) AF: 0.00 AC: 0 AN: 43060

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	8.7
DANN	Benign	0.96
PhyloP100		0.24
PromoterAI		0.0014	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs522444; hg19: chr1-170043904;