chr1-175160899-C-G

Position:

• chr1-175160899-C-G

Variant summary

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

The NM_014656.3(KIAA0040):​c.115G>C​(p.Val39Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000286 in 1,399,338 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000029 (0 hom.)
• Consequence: KIAA0040 NM_014656.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.17

Genes affected

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

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=0.21369249).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIAA0040	NM_014656.3	c.115G>C	p.Val39Leu	missense_variant	4/4	ENST00000423313.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIAA0040	ENST00000423313.6	c.115G>C	p.Val39Leu	missense_variant	4/4	1	NM_014656.3	P1
KIAA0040	ENST00000444639.5	c.115G>C	p.Val39Leu	missense_variant	4/4	1		P1
KIAA0040	ENST00000545251.6	c.115G>C	p.Val39Leu	missense_variant	3/3	1		P1
KIAA0040	ENST00000619513.1	c.-269G>C		5_prime_UTR_variant	2/2	2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000286 AC: 4 AN: 1399338 Hom.: 0 Cov.: 35 AF XY: 0.00000145 AC XY: 1 AN XY: 690170

Gnomad4 AFR exome AF: 0.000127

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: 0.00

GnomAD4 genome Cov.: 31

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

Jun 24, 2022

The c.115G>C (p.V39L) alteration is located in exon 5 (coding exon 1) of the KIAA0040 gene. This alteration results from a G to C substitution at nucleotide position 115, causing the valine (V) at amino acid position 39 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	Benign	0.18
BayesDel_addAF	Benign	-0.047	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	17
DANN	Benign	0.75
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.55	.;.;T
M_CAP	Uncertain	0.090	D
MetaRNN	Benign	0.21	T;T;T
MutationTaster	Benign	0.89	N;N;N
PrimateAI	Benign	0.45	T
Sift4G	Pathogenic	0.0	D;D;D
Vest4		0.39
MVP		0.12
GERP RS		4.7
Varity_R		0.068
gMVP		0.11

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: chr1-175130035;