18-37067113-C-T

Position:

• chr18-37067113-C-T

Variant summary

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

The NM_020776.3(KIAA1328):​c.800C>T​(p.Thr267Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,692 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: KIAA1328 NM_020776.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.694

Genes affected

KIAA1328 (HGNC:29248): (KIAA1328)

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=0.11455241).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIAA1328	NM_020776.3	c.800C>T	p.Thr267Ile	missense_variant	7/10	ENST00000280020.10	NP_065827.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIAA1328	ENST00000280020.10	c.800C>T	p.Thr267Ile	missense_variant	7/10	1	NM_020776.3	ENSP00000280020	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461692 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727128

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: 0.00000180

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

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

Apr 17, 2023

The c.800C>T (p.T267I) alteration is located in exon 7 (coding exon 7) of the KIAA1328 gene. This alteration results from a C to T substitution at nucleotide position 800, causing the threonine (T) at amino acid position 267 to be replaced by an isoleucine (I). 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	Benign	0.11
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	1.4
DANN	Benign	0.96
DEOGEN2	Benign	0.026	T;.
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.70	T;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N;.
MutationTaster	Benign	1.0	D;D;N;N;N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.5	N;.
REVEL	Benign	0.019
Sift	Benign	0.071	T;.
Sift4G	Benign	0.15	T;T
Polyphen		0.047	B;.
Vest4		0.083
MutPred		0.18		Loss of glycosylation at T267 (P = 0.0223);.;
MVP		0.17
MPC		0.070
ClinPred		0.14	T
GERP RS		2.4
Varity_R		0.048
gMVP		0.12

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs912903031; hg19: chr18-34647076;