20-38213269-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001029864.2(KIAA1755):c.3376C>G(p.Pro1126Ala) 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. 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: 33)
• Consequence: KIAA1755 NM_001029864.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0190

Genes affected

KIAA1755 (HGNC:29372): (KIAA1755)

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.048157424).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIAA1755	NM_001029864.2	c.3376C>G	p.Pro1126Ala	missense_variant	14/14	ENST00000279024.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIAA1755	ENST00000279024.9	c.3376C>G	p.Pro1126Ala	missense_variant	14/14	5	NM_001029864.2	P2
KIAA1755	ENST00000460881.5	n.1552C>G		non_coding_transcript_exon_variant	3/3	1
KIAA1755	ENST00000487506.1	n.1328C>G		non_coding_transcript_exon_variant	2/2	1
KIAA1755	ENST00000484362.1	n.1655C>G		non_coding_transcript_exon_variant	5/5	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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 21, 2024

The c.3376C>G (p.P1126A) alteration is located in exon 14 (coding exon 14) of the KIAA1755 gene. This alteration results from a C to G substitution at nucleotide position 3376, causing the proline (P) at amino acid position 1126 to be replaced by an alanine (A). 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	0.059
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.79
Cadd	Benign	0.075
Dann	Benign	0.095
DEOGEN2	Benign	0.0045	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.047	N
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.048	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.6	L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.58	N
REVEL	Benign	0.012
Sift	Benign	0.52	T
Sift4G	Benign	0.28	T
Polyphen		0.0020	B
Vest4		0.10
MutPred		0.13		Loss of glycosylation at P1126 (P = 0.0301);
MVP		0.040
MPC		0.037
ClinPred		0.043	T
GERP RS		-1.1
Varity_R		0.020
gMVP		0.097

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: chr20-36841671;