19-10566005-T-A

Position:

• chr19-10566005-T-A

Variant summary

Our verdict is Likely benign. Variant got -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

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]

KRI1 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRI1	NM_023008.5	c.-6A>T		5_prime_UTR_variant	1/19	ENST00000312962.12	NP_075384.4
KRI1	XM_011528190.3	c.-268A>T		5_prime_UTR_variant	1/18		XP_011526492.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRI1	ENST00000312962.12	c.-6A>T		5_prime_UTR_variant	1/19	1	NM_023008.5	ENSP00000320917.9

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000825

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000187

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 36

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
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
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

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: rs3218222; hg19: chr19-10676681;