1-74026958-A-G

Variant names:

• chr1-74026958-A-G
• rs373510272
• NM_001105659.2:c.1730T>C

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.1730T>C​(p.Ile577Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000144 in 1,392,678 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. 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. I577R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: LRRIQ3 NM_001105659.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.191
• Publications: 1 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=0.041500777).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRIQ3	NM_001105659.2	c.1730T>C	p.Ile577Thr	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.1730T>C	p.Ile577Thr	missense_variant	Exon 8 of 8	5	NM_001105659.2	ENSP00000346414.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000144 AC: 2 AN: 1392678 Hom.: 0 Cov.: 27 AF XY: 0.00000144 AC XY: 1 AN XY: 695224

African (AFR) AF: 0.00 AC: 0 AN: 30932

American (AMR) AF: 0.0000521 AC: 2 AN: 38404

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24950

East Asian (EAS) AF: 0.00 AC: 0 AN: 39024

South Asian (SAS) AF: 0.00 AC: 0 AN: 80832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50546

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5356

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1064776

Other (OTH) AF: 0.00 AC: 0 AN: 57858

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	7.8
DANN	Benign	0.82
DEOGEN2	Benign	0.0010	T;T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.44	.;T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.042	T;T
MetaSVM	Benign	-0.99	T
PhyloP100		0.19
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.043
Sift	Benign	0.30	T;T
Sift4G	Benign	0.44	T;T
Polyphen		0.046	B;B
Vest4		0.058
MutPred		0.26		Loss of stability (P = 0.0103);Loss of stability (P = 0.0103);
MVP		0.15
MPC		0.0038
ClinPred		0.035	T
GERP RS		-1.3
Varity_R		0.042
gMVP		0.018
Mutation Taster		=94/6	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: rs373510272; hg19: chr1-74492642;