19-10555154-C-A

Variant names:

• chr19-10555154-C-A
• NM_023008.5:c.1714G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_023008.5(KRI1):​c.1714G>T​(p.Ala572Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,822 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A572V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: KRI1 NM_023008.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.377
• Publications: 0 publications found

Genes affected

KRI1 (HGNC:25769): (KRI1 homolog) This gene overlaps with the gene for cysteine endopeptidase AUT-like 4 in a head-to-tail orientation. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.069093764).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_023008.5. 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
	KRI1	NM_023008.5	MANE Select	c.1714G>T	p.Ala572Ser	missense	Exon 18 of 19	NP_075384.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRI1	ENST00000312962.12	TSL:1 MANE Select	c.1714G>T	p.Ala572Ser	missense	Exon 18 of 19	ENSP00000320917.9	Q8N9T8
	KRI1	ENST00000906782.1		c.1756G>T	p.Ala586Ser	missense	Exon 18 of 19	ENSP00000576841.1
	KRI1	ENST00000958127.1		c.1738G>T	p.Ala580Ser	missense	Exon 18 of 19	ENSP00000628186.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461822 Hom.: 0 Cov.: 34 AF XY: 0.00000688 AC XY: 5 AN XY: 727224

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53364

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1112008

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 34

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	0.098
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	2.3
DANN	Benign	0.81
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.069	T
MetaSVM	Benign	-0.97	T
PhyloP100		0.38
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.47	N
REVEL	Benign	0.067
Sift	Benign	0.76	T
Sift4G	Benign	0.76	T
Vest4		0.12
MVP		0.28
MPC		0.16
ClinPred		0.39	T
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

hg19: chr19-10665830;