6-127447075-A-C

Position:

• chr6-127447075-A-C

Variant summary

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

The NM_014702.5(KIAA0408):​c.1244T>G​(p.Val415Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,572 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: KIAA0408 NM_014702.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.336

Genes affected

KIAA0408 (HGNC:21636): (KIAA0408)

KIAA0408 (HGNC:):

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=0.08582005).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIAA0408	NM_014702.5	c.1244T>G	p.Val415Gly	missense_variant	5/6	ENST00000483725.8	NP_055517.3
SOGA3-KIAA0408	NR_174482.1	n.5290T>G		non_coding_transcript_exon_variant	12/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIAA0408	ENST00000483725.8	c.1244T>G	p.Val415Gly	missense_variant	5/6	5	NM_014702.5	ENSP00000435150.2
ENSG00000255330	ENST00000481848.6	n.*1565T>G		non_coding_transcript_exon_variant	11/12	5		ENSP00000455908.1
ENSG00000255330	ENST00000481848.6	n.*1565T>G		3_prime_UTR_variant	11/12	5		ENSP00000455908.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461572 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727092

Gnomad4 AFR exome AF: 0.00

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000468 Hom.: 0

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

Aug 16, 2021

The c.1244T>G (p.V415G) alteration is located in exon 5 (coding exon 4) of the KIAA0408 gene. This alteration results from a T to G substitution at nucleotide position 1244, causing the valine (V) at amino acid position 415 to be replaced by a glycine (G). 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	0.086
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	4.3
DANN	Benign	0.97
DEOGEN2	Benign	0.16	.;T
Eigen	Benign	-0.96
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.097	N
LIST_S2	Benign	0.24	T;T
M_CAP	Benign	0.0073	T
MetaRNN	Benign	0.086	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.7	.;L
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-4.4	D;D
REVEL	Benign	0.016
Sift	Pathogenic	0.0	D;D
Sift4G	Uncertain	0.028	D;D
Polyphen		0.010	.;B
Vest4		0.091
MutPred		0.19		.;Loss of stability (P = 0.0047);
MVP		0.17
MPC		0.068
ClinPred		0.32	T
GERP RS		1.4
Varity_R		0.12
gMVP		0.032

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

Other links and lift over

dbSNP: rs1447462142; hg19: chr6-127768220;