NM_001105659.2:c.1843G>A

Variant names:

• chr1-74026845-C-T
• rs199646124
• NM_001105659.2:c.1843G>A

Variant summary

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

The NM_001105659.2(LRRIQ3):​c.1843G>A​(p.Asp615Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000412 in 1,455,796 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. D615H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: LRRIQ3 NM_001105659.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15
• Publications: 0 publications found

Genes affected

LRRIQ3 (HGNC:28318): (leucine rich repeats and IQ motif containing 3)

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=0.03524667).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRIQ3	NM_001105659.2	c.1843G>A	p.Asp615Asn	missense_variant	Exon 8 of 8	ENST00000354431.9	NP_001099129.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRIQ3	ENST00000354431.9	c.1843G>A	p.Asp615Asn	missense_variant	Exon 8 of 8	5	NM_001105659.2	ENSP00000346414.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000816 AC: 2 AN: 245096 AF XY: 0.0000150

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000113

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000412 AC: 6 AN: 1455796 Hom.: 0 Cov.: 29 AF XY: 0.00000276 AC XY: 2 AN XY: 724166

African (AFR) AF: 0.00 AC: 0 AN: 33136

American (AMR) AF: 0.00 AC: 0 AN: 43726

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25970

East Asian (EAS) AF: 0.0000254 AC: 1 AN: 39424

South Asian (SAS) AF: 0.00 AC: 0 AN: 85262

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52908

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5724

European-Non Finnish (NFE) AF: 0.00000361 AC: 4 AN: 1109544

Other (OTH) AF: 0.0000166 AC: 1 AN: 60102

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.00000829 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.66
DANN	Benign	0.35
DEOGEN2	Benign	0.00041	T;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0072	N
LIST_S2	Benign	0.52	.;T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.035	T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.55	N;N
PhyloP100		-1.2
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.12	N;N
REVEL	Benign	0.0040
Sift	Benign	0.84	T;T
Sift4G	Benign	0.88	T;T
Polyphen		0.0	B;B
Vest4		0.072
MutPred		0.23		Gain of MoRF binding (P = 0.0199);Gain of MoRF binding (P = 0.0199);
MVP		0.040
MPC		0.0041
ClinPred		0.017	T
GERP RS		-2.0
Varity_R		0.022
gMVP		0.0047
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: rs199646124; hg19: chr1-74492529;