17-16491923-C-T

Position:

• chr17-16491923-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001113567.3(LRRC75A):​c.68G>A​(p.Arg23Gln) 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LRRC75A NM_001113567.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.25

Genes affected

LRRC75A (HGNC:32403): (leucine rich repeat containing 75A) Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

LOC124903936 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12498367).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRC75A	NM_001113567.3	c.68G>A	p.Arg23Gln	missense_variant	1/4	ENST00000470794.2
LOC124903936	XR_007065641.1	n.1605+4477C>T		intron_variant, non_coding_transcript_variant
LRRC75A	NM_207387.4	c.68G>A	p.Arg23Gln	missense_variant	1/3
LRRC75A	XM_047435962.1	c.68G>A	p.Arg23Gln	missense_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRC75A	ENST00000470794.2	c.68G>A	p.Arg23Gln	missense_variant	1/4	1	NM_001113567.3	P1
LRRC75A	ENST00000409083.7	c.68G>A	p.Arg23Gln	missense_variant	1/3	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1105966 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 534236

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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

Feb 07, 2023

The c.68G>A (p.R23Q) alteration is located in exon 1 (coding exon 1) of the LRRC75A gene. This alteration results from a G to A substitution at nucleotide position 68, causing the arginine (R) at amino acid position 23 to be replaced by a glutamine (Q). 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	0.21
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	23
DANN	Uncertain	0.99
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.67	T;T
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N;N
MutationTaster	Benign	0.97	N;N
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-0.54	N;N
REVEL	Benign	0.044
Sift	Benign	0.063	T;T
Sift4G	Benign	0.12	T;T
Polyphen		0.93	P;P
Vest4		0.090
MutPred		0.20		Loss of MoRF binding (P = 0.0469);Loss of MoRF binding (P = 0.0469);
MVP		0.043
MPC		0.93
ClinPred		0.49	T
GERP RS		1.9
Varity_R		0.081
gMVP		0.33

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

LitVar

Other links and lift over

dbSNP: rs2093858395; hg19: chr17-16395237;