5-94386331-G-C

Variant names:

• chr5-94386331-G-C
• rs72771666
• NM_001145678.3:c.3530C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001145678.3(KIAA0825):​c.3530C>G​(p.Thr1177Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,399,278 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/17 in silico tools predict 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: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: KIAA0825 NM_001145678.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0540

Genes affected

KIAA0825 (HGNC:28532): (KIAA0825)

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=0.0530093).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIAA0825	NM_001145678.3	c.3530C>G	p.Thr1177Arg	missense_variant	Exon 19 of 21	ENST00000682413.1	NP_001139150.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIAA0825	ENST00000682413.1	c.3530C>G	p.Thr1177Arg	missense_variant	Exon 19 of 21		NM_001145678.3	ENSP00000506760.1
KIAA0825	ENST00000703867.1	c.3545C>G	p.Thr1182Arg	missense_variant	Exon 19 of 21			ENSP00000515512.1
KIAA0825	ENST00000513200.7	c.3530C>G	p.Thr1177Arg	missense_variant	Exon 18 of 20	5		ENSP00000424618.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000634 AC: 1 AN: 157762 Hom.: 0 AF XY: 0.0000120 AC XY: 1 AN XY: 83290

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000163

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1399278 Hom.: 0 Cov.: 30 AF XY: 0.00000290 AC XY: 2 AN XY: 690152

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000185

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	1.3
DANN	Benign	0.93
DEOGEN2	Benign	0.0044	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.066	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.053	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.33	N
REVEL	Benign	0.061
Sift	Benign	0.032	D
Sift4G	Uncertain	0.048	D
Polyphen		0.52	P
Vest4		0.10
MutPred		0.20		Gain of helix (P = 0.0117);
MVP		0.11
ClinPred		0.097	T
GERP RS		-3.6
Varity_R		0.14

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs72771666; hg19: chr5-93722036;