22-25028624-C-G

Variant names:

• chr22-25028624-C-G
• rs973340896
• NM_001145206.2:c.625C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. 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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 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
• Publications: 0 publications found

Genes affected

KIAA1671 (HGNC:29345): (KIAA1671)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.11091557).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145206.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIAA1671	NM_001145206.2	MANE Select	c.625C>G	p.Gln209Glu	missense	Exon 3 of 13	NP_001138678.1	Q9BY89-1
	KIAA1671	NM_001386930.1		c.625C>G	p.Gln209Glu	missense	Exon 3 of 12	NP_001373859.1
	KIAA1671	NM_001386932.1		c.625C>G	p.Gln209Glu	missense	Exon 3 of 13	NP_001373861.1	Q9BY89-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIAA1671	ENST00000358431.8	TSL:1 MANE Select	c.625C>G	p.Gln209Glu	missense	Exon 3 of 13	ENSP00000351207.3	Q9BY89-1
	KIAA1671	ENST00000406486.8	TSL:5	c.625C>G	p.Gln209Glu	missense	Exon 4 of 14	ENSP00000385152.3	Q9BY89-1
	KIAA1671	ENST00000910712.1		c.625C>G	p.Gln209Glu	missense	Exon 4 of 14	ENSP00000580771.1

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

African (AFR) AF: 0.00 AC: 0 AN: 31598

American (AMR) AF: 0.000252 AC: 9 AN: 35700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25182

East Asian (EAS) AF: 0.00 AC: 0 AN: 35736

South Asian (SAS) AF: 0.00 AC: 0 AN: 79236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48746

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 0.00000649 AC: 7 AN: 1078942

Other (OTH) AF: 0.0000345 AC: 2 AN: 58000

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000302

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
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
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.62
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.092
Sift	Uncertain	0.027	D
Sift4G	Benign	0.83	T
Polyphen		0.60	P
Vest4		0.16
MutPred		0.13		Loss of helix (P = 0.0138)
MVP		0.27
ClinPred		0.14	T
GERP RS		3.5
Varity_R		0.16
gMVP		0.042
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

dbSNP: rs973340896; hg19: chr22-25424591;