NM_001145206.2:c.1121C>A

Variant names:

• chr22-25029120-C-A
• rs1488913794
• NM_001145206.2:c.1121C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001145206.2(KIAA1671):​c.1121C>A​(p.Ser374*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000763 in 1,311,464 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.6e-7 (0 hom.)
• Consequence: KIAA1671 NM_001145206.2 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.533
• Publications: 0 publications found

Genes affected

KIAA1671 (HGNC:29345): (KIAA1671)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

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.1121C>A	p.Ser374*	stop_gained	Exon 3 of 13	NP_001138678.1	Q9BY89-1
	KIAA1671	NM_001386930.1		c.1121C>A	p.Ser374*	stop_gained	Exon 3 of 12	NP_001373859.1
	KIAA1671	NM_001386932.1		c.1121C>A	p.Ser374*	stop_gained	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.1121C>A	p.Ser374*	stop_gained	Exon 3 of 13	ENSP00000351207.3	Q9BY89-1
	KIAA1671	ENST00000406486.8	TSL:5	c.1121C>A	p.Ser374*	stop_gained	Exon 4 of 14	ENSP00000385152.3	Q9BY89-1
	KIAA1671	ENST00000910712.1		c.1121C>A	p.Ser374*	stop_gained	Exon 4 of 14	ENSP00000580771.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.63e-7 AC: 1 AN: 1311464 Hom.: 0 Cov.: 51 AF XY: 0.00 AC XY: 0 AN XY: 637284

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 28560

American (AMR) AF: 0.00 AC: 0 AN: 21040

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19294

East Asian (EAS) AF: 0.00 AC: 0 AN: 35012

South Asian (SAS) AF: 0.00 AC: 0 AN: 63960

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45956

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5272

European-Non Finnish (NFE) AF: 9.63e-7 AC: 1 AN: 1038264

Other (OTH) AF: 0.00 AC: 0 AN: 54106

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.34	D
BayesDel_noAF	Pathogenic	0.25
CADD	Pathogenic	33
DANN	Uncertain	0.99
Eigen	Benign	0.049
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.16	N
PhyloP100		0.53
Vest4		0.061
GERP RS		2.5
Mutation Taster		=17/183	disease causing (fs/PTC)

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: rs1488913794; hg19: chr22-25425087;