rs3218222

Variant names:

• chr19-10566005-T-A
• rs3218222
• NM_023008.5:c.-6A>T

Your query was ambiguous. Multiple possible variants found:

• chr19-10566005-T-A
• chr19-10566005-T-C
• chr19-10566005-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_023008.5(KRI1):​c.-6A>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000294 in 1,360,274 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 36)
  • Exomes 𝑓: 0.0000029 (0 hom.)
• Consequence: KRI1 NM_023008.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.65
• Publications: 43 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.036797673).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRI1	NM_023008.5	MANE Select	c.-6A>T		5_prime_UTR	Exon 1 of 19	NP_075384.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRI1	ENST00000312962.12	TSL:1 MANE Select	c.-6A>T		5_prime_UTR	Exon 1 of 19	ENSP00000320917.9
	KRI1	ENST00000652042.1		c.13A>T	p.Thr5Ser	missense	Exon 1 of 19	ENSP00000498803.1
	KRI1	ENST00000537964.5	TSL:4	n.6A>T		non_coding_transcript_exon	Exon 1 of 7

Frequencies

GnomAD3 genomes Cov.: 36

GnomAD4 exome AF: 0.00000294 AC: 4 AN: 1360274 Hom.: 0 Cov.: 64 AF XY: 0.00000298 AC XY: 2 AN XY: 670608

African (AFR) AF: 0.00 AC: 0 AN: 28250

American (AMR) AF: 0.00 AC: 0 AN: 32500

Ashkenazi Jewish (ASJ) AF: 0.0000825 AC: 2 AN: 24228

East Asian (EAS) AF: 0.00 AC: 0 AN: 33250

South Asian (SAS) AF: 0.00 AC: 0 AN: 76720

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36164

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4090

European-Non Finnish (NFE) AF: 0.00000187 AC: 2 AN: 1068486

Other (OTH) AF: 0.00 AC: 0 AN: 56586

GnomAD4 genome Cov.: 36

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	16
DANN	Benign	0.83
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.044	N
LIST_S2	Benign	0.20	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.037	T
MetaSVM	Benign	-0.95	T
PhyloP100		1.6
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	0.36	N
REVEL	Benign	0.010
Sift	Benign	0.49	T
Sift4G	Benign	0.14	T
Vest4		0.026
MVP		0.13
MPC		0.14
ClinPred		0.47	T
GERP RS		3.3
PromoterAI		0.15	Neutral
Mutation Taster		=297/3	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: rs3218222; hg19: chr19-10676681;