chr5-176347791-C-A

Variant names:

• chr5-176347791-C-A
• rs757621868
• NM_020444.5:c.727G>T

Variant summary

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

The NM_020444.5(KIAA1191):​c.727G>T​(p.Ala243Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000207 in 1,449,794 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A243T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: KIAA1191 NM_020444.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.469
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.038449764).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIAA1191	NM_020444.5	c.727G>T	p.Ala243Ser	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.727G>T	p.Ala243Ser	missense_variant	Exon 9 of 9	1	NM_020444.5	ENSP00000298569.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000207 AC: 3 AN: 1449794 Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1 AN XY: 720188

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 32906

American (AMR) AF: 0.00 AC: 0 AN: 42822

Ashkenazi Jewish (ASJ) AF: 0.0000791 AC: 2 AN: 25286

East Asian (EAS) AF: 0.00 AC: 0 AN: 39562

South Asian (SAS) AF: 0.00 AC: 0 AN: 84556

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53024

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5678

European-Non Finnish (NFE) AF: 9.04e-7 AC: 1 AN: 1106208

Other (OTH) AF: 0.00 AC: 0 AN: 59752

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	8.0
DANN	Benign	0.85
DEOGEN2	Benign	0.010	T;.;.;.;T
Eigen	Benign	-0.87
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.85	.;.;D;T;D
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.038	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L;.;.;.;L
PhyloP100		-0.47
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.47	N;N;.;.;N
REVEL	Benign	0.067
Sift	Benign	0.58	T;T;.;.;T
Sift4G	Benign	0.96	T;T;T;T;T
Polyphen		0.0070	B;.;.;.;B
Vest4		0.060
MutPred		0.15		Gain of phosphorylation at A243 (P = 0.0405);.;.;.;Gain of phosphorylation at A243 (P = 0.0405);
MVP		0.24
MPC		0.26
ClinPred		0.053	T
GERP RS		-2.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.030
gMVP		0.11
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs757621868; hg19: chr5-175774794;