12-85038190-A-T

Position:

• chr12-85038190-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001079910.2(LRRIQ1):​c.14A>T​(p.Asp5Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000707 in 1,414,144 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: LRRIQ1 NM_001079910.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.94

Genes affected

LRRIQ1 (HGNC:25708): (leucine rich repeats and IQ motif containing 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30435002).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRIQ1	NM_001079910.2	c.14A>T	p.Asp5Val	missense_variant	2/27	ENST00000393217.7	NP_001073379.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRIQ1	ENST00000393217.7	c.14A>T	p.Asp5Val	missense_variant	2/27	1	NM_001079910.2	ENSP00000376910	P1
LRRIQ1	ENST00000529408.1	n.109A>T		non_coding_transcript_exon_variant	2/6	1
LRRIQ1	ENST00000393212.7	c.14A>T	p.Asp5Val	missense_variant	2/6	4		ENSP00000376906
LRRIQ1	ENST00000525971.6	n.132A>T		non_coding_transcript_exon_variant	2/17	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.07e-7 AC: 1 AN: 1414144 Hom.: 0 Cov.: 30 AF XY: 0.00000142 AC XY: 1 AN XY: 703698

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000403

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 06, 2021

The c.14A>T (p.D5V) alteration is located in exon 2 (coding exon 1) of the LRRIQ1 gene. This alteration results from a A to T substitution at nucleotide position 14, causing the aspartic acid (D) at amino acid position 5 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.0080	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.069	.;T
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.67	T;T
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.30	T;T
MetaSVM	Benign	-0.69	T
MutationAssessor	Uncertain	2.5	.;M
MutationTaster	Benign	1.0	D
PrimateAI	Benign	0.45	T
PROVEAN	Pathogenic	-6.0	D;D
REVEL	Benign	0.19
Sift	Uncertain	0.018	D;D
Sift4G	Uncertain	0.0020	D;D
Polyphen		0.98	.;D
Vest4		0.41
MutPred		0.18		Gain of helix (P = 0.132);Gain of helix (P = 0.132);
MVP		0.61
MPC		0.058
ClinPred		0.99	D
GERP RS		4.9
Varity_R		0.35
gMVP		0.12

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-85431968;