17-64859494-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_199340.5(LRRC37A3):c.4652A>T(p.Tyr1551Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: LRRC37A3 NM_199340.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.135

Genes affected

LRRC37A3 (HGNC:32427): (leucine rich repeat containing 37 member A3) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

LOC105376844 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, LRRC37A3
• BP4: Computational evidence support a benign effect (MetaRNN=0.15748766).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRC37A3	NM_199340.5	c.4652A>T	p.Tyr1551Phe	missense_variant	12/15	ENST00000584306.6
LOC105376844	XR_934912.4	n.177+9507T>A		intron_variant, non_coding_transcript_variant
LRRC37A3	NM_001303255.3	c.2006A>T	p.Tyr669Phe	missense_variant	8/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRC37A3	ENST00000584306.6	c.4652A>T	p.Tyr1551Phe	missense_variant	12/15	1	NM_199340.5	P1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 30

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 05, 2023

The c.4652A>T (p.Y1551F) alteration is located in exon 11 (coding exon 9) of the LRRC37A3 gene. This alteration results from a A to T substitution at nucleotide position 4652, causing the tyrosine (Y) at amino acid position 1551 to be replaced by a phenylalanine (F). 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	0.18
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
Cadd	Benign	15
Dann	Benign	0.93
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.015	N
LIST_S2	Uncertain	0.86	D;D;D;D;.;D
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.16	T;T;T;T;T;T
MetaSVM	Benign	-0.85	T
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Pathogenic	0.83	D
REVEL	Benign	0.057
Sift4G	Uncertain	0.0050	D;D;D;D;D;D
Polyphen		0.96	.;.;.;P;P;.
Vest4		0.25
MutPred		0.28		.;.;.;Loss of phosphorylation at Y1551 (P = 0.0528);Loss of phosphorylation at Y1551 (P = 0.0528);.;
MVP		0.11
ClinPred		0.45	T
GERP RS		1.2
Varity_R		0.16
gMVP		0.037

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-62855612;