20-38213103-C-T

Variant summary

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

The NM_001029864.2(KIAA1755):c.3542G>A(p.Gly1181Glu) 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: 1.75

Genes affected

KIAA1755 (HGNC:29372): (KIAA1755)

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=0.08440468).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIAA1755	NM_001029864.2	c.3542G>A	p.Gly1181Glu	missense_variant	14/14	ENST00000279024.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIAA1755	ENST00000279024.9	c.3542G>A	p.Gly1181Glu	missense_variant	14/14	5	NM_001029864.2	P2
KIAA1755	ENST00000460881.5	n.1718G>A		non_coding_transcript_exon_variant	3/3	1
KIAA1755	ENST00000487506.1	n.1494G>A		non_coding_transcript_exon_variant	2/2	1
KIAA1755	ENST00000484362.1	n.1821G>A		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

Oct 27, 2021

The c.3542G>A (p.G1181E) alteration is located in exon 14 (coding exon 14) of the KIAA1755 gene. This alteration results from a G to A substitution at nucleotide position 3542, causing the glycine (G) at amino acid position 1181 to be replaced by a glutamic acid (E). 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	0.14
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
Cadd	Benign	20
Dann	Benign	0.92
DEOGEN2	Benign	0.0051	T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.0098	T
MetaRNN	Benign	0.084	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L
MutationTaster	Benign	0.64	D
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.14
Sift	Benign	0.15	T
Sift4G	Benign	0.23	T
Polyphen		0.35	B
Vest4		0.30
MutPred		0.15		Loss of glycosylation at S1178 (P = 0.1254);
MVP		0.19
MPC		0.29
ClinPred		0.51	D
GERP RS		2.8
Varity_R		0.069
gMVP		0.16

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: chr20-36841505; COSMIC: COSV54073768; COSMIC: COSV54073768;