6-17764562-C-T

Position:

• chr6-17764562-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_022113.6(KIF13A):​c.4966G>A​(p.Glu1656Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00314 in 1,613,890 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0025 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0032 (16 hom.)
• Consequence: KIF13A NM_022113.6 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.05

Genes affected

KIF13A (HGNC:14566): (kinesin family member 13A) This gene encodes a member of the kinesin family of microtubule-based motor proteins that function in the positioning of endosomes. This family member can direct mannose-6-phosphate receptor-containing vesicles from the trans-Golgi network to the plasma membrane, and it is necessary for the steady-state distribution of late endosomes/lysosomes. It is also required for the translocation of FYVE-CENT and TTC19 from the centrosome to the midbody during cytokinesis, and it plays a role in melanosome maturation. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Aug 2011]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0048267543).
• BP6: Variant 6-17764562-C-T is Benign according to our data. Variant chr6-17764562-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2656260.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-17764562-C-T is described in Lovd as [Likely_benign].
• BS2: High Homozygotes in GnomAdExome4 at 16 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF13A	NM_022113.6	c.4966G>A	p.Glu1656Lys	missense_variant	39/39	ENST00000259711.11	NP_071396.4
KIF13A	NM_001105566.3	c.4861G>A	p.Glu1621Lys	missense_variant	38/38		NP_001099036.1
KIF13A	NM_001105567.3	c.4822G>A	p.Glu1608Lys	missense_variant	37/37		NP_001099037.1
KIF13A	NM_001105568.4	c.4822G>A	p.Glu1608Lys	missense_variant	37/38		NP_001099038.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF13A	ENST00000259711.11	c.4966G>A	p.Glu1656Lys	missense_variant	39/39	1	NM_022113.6	ENSP00000259711.6

Frequencies

GnomAD3 genomes AF: 0.00246 AC: 374 AN: 152074 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000314

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00151

Gnomad ASJ AF: 0.00260

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00373

Gnomad FIN AF: 0.000567

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00437

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.00282 AC: 702 AN: 249102 Hom.: 6 AF XY: 0.00310 AC XY: 419 AN XY: 135126

Gnomad AFR exome AF: 0.000452

Gnomad AMR exome AF: 0.00154

Gnomad ASJ exome AF: 0.00288

Gnomad EAS exome AF: 0.000111

Gnomad SAS exome AF: 0.00471

Gnomad FIN exome AF: 0.000464

Gnomad NFE exome AF: 0.00391

Gnomad OTH exome AF: 0.00265

GnomAD4 exome AF: 0.00321 AC: 4690 AN: 1461698 Hom.: 16 Cov.: 34 AF XY: 0.00330 AC XY: 2401 AN XY: 727132

Gnomad4 AFR exome AF: 0.000508

Gnomad4 AMR exome AF: 0.00159

Gnomad4 ASJ exome AF: 0.00226

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00527

Gnomad4 FIN exome AF: 0.000524

Gnomad4 NFE exome AF: 0.00344

Gnomad4 OTH exome AF: 0.00311

GnomAD4 genome AF: 0.00246 AC: 374 AN: 152192 Hom.: 0 Cov.: 32 AF XY: 0.00215 AC XY: 160 AN XY: 74404

Gnomad4 AFR AF: 0.000313

Gnomad4 AMR AF: 0.00150

Gnomad4 ASJ AF: 0.00260

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00373

Gnomad4 FIN AF: 0.000567

Gnomad4 NFE AF: 0.00437

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00379 Hom.: 2

Bravo AF: 0.00230

TwinsUK AF: 0.00270 AC: 10

ALSPAC AF: 0.00182 AC: 7

ESP6500AA AF: 0.000500 AC: 2

ESP6500EA AF: 0.00443 AC: 37

ExAC AF: 0.00282 AC: 341

EpiCase AF: 0.00534

EpiControl AF: 0.00605

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2023

KIF13A: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.023	.;T;T;.;.;T
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.074
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.93	D;D;D;D;D;D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.0048	T;T;T;T;T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	1.8	.;.;L;.;.;.
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.49	N;N;N;N;N;.
REVEL	Benign	0.20
Sift	Benign	0.058	T;D;D;T;D;.
Sift4G	Benign	0.82	T;T;T;T;T;.
Polyphen		0.19	B;.;P;P;P;.
Vest4		0.33
MVP		0.59
MPC		0.29
ClinPred		0.022	T
GERP RS		6.1
Varity_R		0.11
gMVP		0.40

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: rs41267710; hg19: chr6-17764793; COSMIC: COSV99439350;