Variant 20-38213732-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001029864.2(KIAA1755):c.2913C>A(p.Phe971Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000227 in 1,322,598 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)

Exomes 𝑓: 0.0000023 ( 0 hom. )

Consequence

KIAA1755
NM_001029864.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.31

Variant links:

Genes affected

KIAA1755 (HGNC:29372): (KIAA1755)

KIAA1755 links:

KIAA1755 (HGNC:):

KIAA1755 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3598435).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIAA1755	NM_001029864.2 linkuse as main transcript	c.2913C>A	p.Phe971Leu	missense_variant	14/14	ENST00000279024.9	NP_001025035.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KIAA1755	ENST00000279024.9 linkuse as main transcript	c.2913C>A	p.Phe971Leu	missense_variant	14/14	5	NM_001029864.2	ENSP00000279024.4	Q5JYT7
KIAA1755	ENST00000460881.5 linkuse as main transcript	n.1089C>A		non_coding_transcript_exon_variant	3/3	1
KIAA1755	ENST00000487506.1 linkuse as main transcript	n.865C>A		non_coding_transcript_exon_variant	2/2	1
KIAA1755	ENST00000484362.1 linkuse as main transcript	n.1192C>A		non_coding_transcript_exon_variant	5/5	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000177

AC:

AN:

112908

Hom.:

AF XY:

0.0000173

AC XY:

AN XY:

57900

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000165

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000227

AC:

AN:

1322598

Hom.:

Cov.:

AF XY:

0.00000155

AC XY:

AN XY:

643562

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000801

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 21, 2023

The c.2913C>A (p.F971L) alteration is located in exon 14 (coding exon 14) of the KIAA1755 gene. This alteration results from a C to A substitution at nucleotide position 2913, causing the phenylalanine (F) at amino acid position 971 to be replaced by a leucine (L). 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

Pathogenic

0.97

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0064

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Benign

0.64

LIST_S2

Benign

0.73

M_CAP

Benign

0.0078

MetaRNN

Benign

0.36

MetaSVM

Benign

-1.1

MutationAssessor

Benign

2.0

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-2.2

REVEL

Benign

0.19

Sift

Benign

0.39

Sift4G

Benign

0.26

Polyphen

1.0

Vest4

0.43

MutPred

0.58

Gain of disorder (P = 0.0931);

MVP

0.36

MPC

0.29

ClinPred

0.80

GERP RS

4.2

Varity_R

0.11

gMVP

0.25

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over