chr17-16447957-C-T

Position:

• chr17-16447957-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.379G>A​(p.Gly127Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000143 in 1,398,756 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: 0.0000014 (0 hom.)
• Consequence: LRRC75A NM_001113567.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.67

Genes affected

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

LRRC75A (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=0.14840889).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC75A	NM_001113567.3	c.379G>A	p.Gly127Ser	missense_variant	3/4	ENST00000470794.2	NP_001107039.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC75A	ENST00000470794.2	c.379G>A	p.Gly127Ser	missense_variant	3/4	1	NM_001113567.3	ENSP00000419502.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1398756 Hom.: 0 Cov.: 31 AF XY: 0.00000145 AC XY: 1 AN XY: 689922

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: 0.00000185

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

Nov 17, 2023

The c.379G>A (p.G127S) alteration is located in exon 3 (coding exon 3) of the LRRC75A gene. This alteration results from a G to A substitution at nucleotide position 379, causing the glycine (G) at amino acid position 127 to be replaced by a serine (S). 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	0.13
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0084	T
Eigen	Benign	0.16
Eigen_PC	Benign	0.12
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.8	L
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.12
Sift	Benign	0.28	T
Sift4G	Benign	0.40	T
Polyphen		0.94	P
Vest4		0.33
MutPred		0.29		Loss of catalytic residue at G127 (P = 0.0024);
MVP		0.043
MPC		0.69
ClinPred		0.82	D
GERP RS		5.2
Varity_R		0.090
gMVP		0.55

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: chr17-16351271;