rs912903031

Variant names:

• chr18-37067113-C-T
• rs912903031
• NM_020776.3:c.800C>T

Variant summary

Our verdict is Uncertain significance. The variant received 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. 16/22 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
• Publications: 0 publications found

Genes affected

KIAA1328 (HGNC:29248): (KIAA1328)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11455241).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020776.3. 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
	KIAA1328	NM_020776.3	MANE Select	c.800C>T	p.Thr267Ile	missense	Exon 7 of 10	NP_065827.1	Q86T90-1
	KIAA1328	NM_001353918.2		c.788C>T	p.Thr263Ile	missense	Exon 7 of 10	NP_001340847.1
	KIAA1328	NM_001322327.2		c.476C>T	p.Thr159Ile	missense	Exon 6 of 10	NP_001309256.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIAA1328	ENST00000280020.10	TSL:1 MANE Select	c.800C>T	p.Thr267Ile	missense	Exon 7 of 10	ENSP00000280020.5	Q86T90-1
	KIAA1328	ENST00000591619.5	TSL:1	c.788C>T	p.Thr263Ile	missense	Exon 7 of 11	ENSP00000465550.1	Q86T90-2
	KIAA1328	ENST00000586135.1	TSL:1	c.-53C>T		5_prime_UTR	Exon 4 of 9	ENSP00000467507.1	Q86T90-3

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

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111860

Other (OTH) AF: 0.0000166 AC: 1 AN: 60374

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.69
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.019
Sift	Benign	0.071	T
Sift4G	Benign	0.15	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
PromoterAI		0.0080	Neutral
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

Other links and lift over

dbSNP: rs912903031; hg19: chr18-34647076;