6-127446606-C-G

Position:

• chr6-127446606-C-G

Variant summary

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

The NM_014702.5(KIAA0408):​c.1713G>C​(p.Glu571Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,824 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: KIAA0408 NM_014702.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.576

Genes affected

KIAA0408 (HGNC:21636): (KIAA0408)

ENSG00000255330 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIAA0408	NM_014702.5	c.1713G>C	p.Glu571Asp	missense_variant	5/6	ENST00000483725.8	NP_055517.3
SOGA3-KIAA0408	NR_174482.1	n.5759G>C		non_coding_transcript_exon_variant	12/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIAA0408	ENST00000483725.8	c.1713G>C	p.Glu571Asp	missense_variant	5/6	5	NM_014702.5	ENSP00000435150.2
ENSG00000255330	ENST00000481848.6	n.*2034G>C		non_coding_transcript_exon_variant	11/12	5		ENSP00000455908.1
ENSG00000255330	ENST00000481848.6	n.*2034G>C		3_prime_UTR_variant	11/12	5		ENSP00000455908.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1461824 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727216

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: 0.00000809

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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

Apr 01, 2024

The c.1713G>C (p.E571D) alteration is located in exon 5 (coding exon 4) of the KIAA0408 gene. This alteration results from a G to C substitution at nucleotide position 1713, causing the glutamic acid (E) at amino acid position 571 to be replaced by an aspartic acid (D). 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	Uncertain	0.37
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.22	T
Eigen	Benign	0.029
Eigen_PC	Benign	-0.097
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.023	T
MetaRNN	Uncertain	0.74	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.14
Sift	Benign	0.049	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.56
MutPred		0.70		Gain of loop (P = 0.0079);
MVP		0.48
MPC		0.066
ClinPred		0.54	D
GERP RS		1.5
Varity_R		0.068
gMVP		0.19

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: chr6-127767751;