chr5-176347653-C-T

Variant names:

• chr5-176347653-C-T
• rs751606711
• NM_020444.5:c.865G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_020444.5(KIAA1191):​c.865G>A​(p.Ala289Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000122 in 1,562,786 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000012 (1 hom.)
• Consequence: KIAA1191 NM_020444.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0410
• 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]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.018256932).
• BP6: Variant 5-176347653-C-T is Benign according to our data. Variant chr5-176347653-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3863697.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.865G>A	p.Ala289Thr	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.865G>A	p.Ala289Thr	missense_variant	Exon 9 of 9	1	NM_020444.5	ENSP00000298569.4

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152102 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000532 AC: 11 AN: 206646 AF XY: 0.0000364

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000411

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000121 AC: 17 AN: 1410684 Hom.: 1 Cov.: 31 AF XY: 0.0000100 AC XY: 7 AN XY: 697514

African (AFR) AF: 0.00 AC: 0 AN: 31590

American (AMR) AF: 0.000363 AC: 13 AN: 35814

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22428

East Asian (EAS) AF: 0.00 AC: 0 AN: 39366

South Asian (SAS) AF: 0.00 AC: 0 AN: 76310

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51642

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5486

European-Non Finnish (NFE) AF: 0.00000367 AC: 4 AN: 1089792

Other (OTH) AF: 0.00 AC: 0 AN: 58256

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152102 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74294

African (AFR) AF: 0.00 AC: 0 AN: 41426

American (AMR) AF: 0.000131 AC: 2 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68012

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.0000156 Hom.: 0

Bravo AF: 0.0000567

ExAC AF: 0.0000412 AC: 5

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Dec 14, 2024

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	0.065
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	8.1
DANN	Benign	0.62
DEOGEN2	Benign	0.0065	T;.;.;.;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.056	N
LIST_S2	Benign	0.57	.;.;T;T;T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.018	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.0	N;.;.;.;N
PhyloP100		0.041
PrimateAI	Benign	0.25	T
PROVEAN	Benign	1.3	N;N;.;.;N
REVEL	Benign	0.20
Sift	Benign	1.0	T;T;.;.;T
Sift4G	Benign	0.64	T;T;T;T;T
Polyphen		0.0	B;.;.;.;B
Vest4		0.015
MutPred		0.090		Gain of relative solvent accessibility (P = 0.0215);.;.;.;Gain of relative solvent accessibility (P = 0.0215);
MVP		0.14
MPC		0.26
ClinPred		0.023	T
GERP RS		-4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.016
gMVP		0.085
Mutation Taster		=100/0	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: rs751606711; hg19: chr5-175774656;