1-35441109-T-G

Position:

• chr1-35441109-T-G

Variant summary

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

The NM_024874.5(KIAA0319L):​c.2900A>C​(p.Lys967Thr) variant causes a missense 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: KIAA0319L NM_024874.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.75

Genes affected

KIAA0319L (HGNC:30071): (KIAA0319 like) Predicted to act upstream of or within several processes, including flagellated sperm motility; proacrosomal vesicle fusion; and receptor-mediated endocytosis of virus by host cell. Located in Golgi apparatus; cytoplasmic vesicle; and nucleolus. [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=0.2141456).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIAA0319L	NM_024874.5	c.2900A>C	p.Lys967Thr	missense_variant	20/21	ENST00000325722.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIAA0319L	ENST00000325722.8	c.2900A>C	p.Lys967Thr	missense_variant	20/21	1	NM_024874.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 10, 2022

The c.2900A>C (p.K967T) alteration is located in exon 20 (coding exon 19) of the KIAA0319L gene. This alteration results from a A to C substitution at nucleotide position 2900, causing the lysine (K) at amino acid position 967 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	T;.;T
Eigen	Benign	0.037
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.92	D;D;D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.21	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	M;.;.
MutationTaster	Benign	0.96	D;D
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-3.6	D;D;D
REVEL	Benign	0.088
Sift	Uncertain	0.0030	D;D;D
Sift4G	Uncertain	0.0060	D;D;.
Polyphen		0.32	B;.;.
Vest4		0.30
MutPred		0.41		Loss of methylation at K967 (P = 0.0021);.;Loss of methylation at K967 (P = 0.0021);
MVP		0.28
MPC		0.51
ClinPred		0.96	D
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.25
gMVP		0.35

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: chr1-35906710;