Variant chr1-175160742-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_014656.3(KIAA0040):c.272T>C(p.Met91Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000826 in 1,548,982 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00049 ( 2 hom., cov: 32)

Exomes 𝑓: 0.000038 ( 0 hom. )

Consequence

KIAA0040
NM_014656.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.45

Variant links:

Genes affected

KIAA0040 (HGNC:28950): (KIAA0040) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

KIAA0040 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.041621476).

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIAA0040	NM_014656.3 linkuse as main transcript	c.272T>C	p.Met91Thr	missense_variant	4/4	ENST00000423313.6	NP_055471.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
KIAA0040	ENST00000423313.6 linkuse as main transcript	c.272T>C	p.Met91Thr	missense_variant	4/4	1	NM_014656.3	ENSP00000462172	P1
KIAA0040	ENST00000444639.5 linkuse as main transcript	c.272T>C	p.Met91Thr	missense_variant	4/4	1		ENSP00000463734	P1
KIAA0040	ENST00000545251.6 linkuse as main transcript	c.272T>C	p.Met91Thr	missense_variant	3/3	1		ENSP00000464040	P1
KIAA0040	ENST00000619513.1 linkuse as main transcript	c.-112T>C		5_prime_UTR_variant	2/2	2		ENSP00000478803

Frequencies

GnomAD3 genomes

AF:

0.000493

AC:

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00174

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000649

AC:

AN:

153998

Hom.:

AF XY:

0.0000245

AC XY:

AN XY:

81642

show subpopulations

Gnomad AFR exome

AF:

0.00125

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

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:

0.0000379

AC:

AN:

1396820

Hom.:

Cov.:

AF XY:

0.0000290

AC XY:

AN XY:

688954

show subpopulations

Gnomad4 AFR exome

AF:

0.00159

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:

0.00

Gnomad4 OTH exome

AF:

0.0000519

GnomAD4 genome

AF:

0.000493

AC:

AN:

152162

Hom.:

Cov.:

AF XY:

0.000565

AC XY:

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.00174

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000150

Hom.:

Bravo

AF:

0.000408

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00145

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000123

AC:

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

Mar 24, 2023

The c.272T>C (p.M91T) alteration is located in exon 5 (coding exon 1) of the KIAA0040 gene. This alteration results from a T to C substitution at nucleotide position 272, causing the methionine (M) at amino acid position 91 to be replaced by a threonine (T). 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

0.61

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Benign

0.94

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.53

.;.;T

M_CAP

Uncertain

0.19

MetaRNN

Benign

0.042

T;T;T

MutationTaster

Benign

0.80

N;N;N

PrimateAI

Uncertain

0.60

Sift4G

Uncertain

0.012

D;D;D

Vest4

0.28

MVP

0.22

GERP RS

5.6

Varity_R

0.33

gMVP

0.040

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