NM_020444.5:c.785G>A

Variant names:

• chr5-176347733-C-T
• rs370474215
• NM_020444.5:c.785G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_020444.5(KIAA1191):​c.785G>A​(p.Arg262Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000957 in 1,609,938 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000092 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000096 (0 hom.)
• Consequence: KIAA1191 NM_020444.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.05
• Publications: 0 publications found

Genes affected

KIAA1191 (HGNC:29209): (KIAA1191) Predicted to enable oxidoreductase activity. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000250909 (HGNC:41234):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.01214534).
• BP6: Variant 5-176347733-C-T is Benign according to our data. Variant chr5-176347733-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2211515.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIAA1191	NM_020444.5	c.785G>A	p.Arg262Gln	missense_variant	Exon 9 of 9	ENST00000298569.9	NP_065177.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIAA1191	ENST00000298569.9	c.785G>A	p.Arg262Gln	missense_variant	Exon 9 of 9	1	NM_020444.5	ENSP00000298569.4

Frequencies

GnomAD3 genomes AF: 0.0000920 AC: 14 AN: 152112 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00375

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000137 AC: 34 AN: 247352 AF XY: 0.000157

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00255

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000713

Gnomad OTH exome AF: 0.000167

GnomAD4 exome AF: 0.0000960 AC: 140 AN: 1457826 Hom.: 0 Cov.: 31 AF XY: 0.000109 AC XY: 79 AN XY: 725046

African (AFR) AF: 0.00 AC: 0 AN: 33272

American (AMR) AF: 0.00 AC: 0 AN: 43872

Ashkenazi Jewish (ASJ) AF: 0.00321 AC: 83 AN: 25882

East Asian (EAS) AF: 0.00 AC: 0 AN: 39676

South Asian (SAS) AF: 0.0000351 AC: 3 AN: 85546

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53310

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5738

European-Non Finnish (NFE) AF: 0.0000378 AC: 42 AN: 1110338

Other (OTH) AF: 0.000199 AC: 12 AN: 60192

GnomAD4 genome AF: 0.0000920 AC: 14 AN: 152112 Hom.: 0 Cov.: 32 AF XY: 0.000135 AC XY: 10 AN XY: 74286

African (AFR) AF: 0.00 AC: 0 AN: 41432

American (AMR) AF: 0.00 AC: 0 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00375 AC: 13 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.000280 Hom.: 0

Bravo AF: 0.000102

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000581 AC: 5

ExAC AF: 0.000148 AC: 18

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Dec 27, 2022

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	16
DANN	Benign	0.88
DEOGEN2	Benign	0.069	T;.;.;.;T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.57
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.71	.;.;T;T;T
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.012	T;T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.8	M;.;.;.;M
PhyloP100		3.0
PrimateAI	Benign	0.24	T
PROVEAN	Uncertain	-2.4	N;N;.;.;N
REVEL	Benign	0.11
Sift	Benign	0.066	T;T;.;.;T
Sift4G	Benign	0.26	T;T;T;T;T
Polyphen		0.62	P;.;.;.;P
Vest4		0.13
MVP		0.36
MPC		0.35
ClinPred		0.10	T
GERP RS		3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.069
gMVP		0.24
Mutation Taster		=78/22	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: rs370474215; hg19: chr5-175774736;