chr22-25028624-C-G

Position:

• chr22-25028624-C-G

Variant summary

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

The NM_001145206.2(KIAA1671):​c.625C>G​(p.Gln209Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000129 in 1,398,838 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: KIAA1671 NM_001145206.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.622

Genes affected

KIAA1671 (HGNC:29345): (KIAA1671)

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=0.11091557).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIAA1671	NM_001145206.2	c.625C>G	p.Gln209Glu	missense_variant	3/13	ENST00000358431.8	NP_001138678.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIAA1671	ENST00000358431.8	c.625C>G	p.Gln209Glu	missense_variant	3/13	1	NM_001145206.2	ENSP00000351207.3
KIAA1671	ENST00000406486.8	c.625C>G	p.Gln209Glu	missense_variant	4/14	5		ENSP00000385152.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000129 AC: 18 AN: 1398838 Hom.: 0 Cov.: 54 AF XY: 0.0000116 AC XY: 8 AN XY: 689974

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000252

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: 0.00000649

Gnomad4 OTH exome AF: 0.0000345

GnomAD4 genome Cov.: 33

Bravo AF: 0.0000302

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 10, 2022

The c.625C>G (p.Q209E) alteration is located in exon 1 (coding exon 1) of the KIAA1671 gene. This alteration results from a C to G substitution at nucleotide position 625, causing the glutamine (Q) at amino acid position 209 to be replaced by a glutamic acid (E). 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	0.088
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	14
DANN	Benign	0.92
DEOGEN2	Benign	0.020	T;T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.054	N
LIST_S2	Benign	0.47	.;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L;L
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.092
Sift	Uncertain	0.027	D;D
Sift4G	Benign	0.83	T;T
Polyphen		0.60	P;P
Vest4		0.16
MutPred		0.13		Loss of helix (P = 0.0138);Loss of helix (P = 0.0138);
MVP		0.27
ClinPred		0.14	T
GERP RS		3.5
Varity_R		0.16
gMVP		0.042

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: rs973340896; hg19: chr22-25424591;