17-16462272-G-A

Variant summary

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

The NM_001113567.3(LRRC75A):​c.361C>T​(p.His121Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,613,980 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

LRRC75A
NM_001113567.3 missense

Scores

1
10
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.37
Variant links:
Genes affected
LRRC75A (HGNC:32403): (leucine rich repeat containing 75A) Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]
SNHG29 (HGNC:28619): (small nucleolar RNA host gene 29)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
LRRC75ANM_001113567.3 linkuse as main transcriptc.361C>T p.His121Tyr missense_variant 2/4 ENST00000470794.2 NP_001107039.1 Q8NAA5-1B7ZMA3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
LRRC75AENST00000470794.2 linkuse as main transcriptc.361C>T p.His121Tyr missense_variant 2/41 NM_001113567.3 ENSP00000419502.1 Q8NAA5-1

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152202
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000718
AC:
18
AN:
250652
Hom.:
0
AF XY:
0.0000590
AC XY:
8
AN XY:
135606
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000492
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000164
GnomAD4 exome
AF:
0.0000157
AC:
23
AN:
1461778
Hom.:
0
Cov.:
31
AF XY:
0.0000138
AC XY:
10
AN XY:
727202
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000515
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
AF:
0.0000131
AC:
2
AN:
152202
Hom.:
0
Cov.:
33
AF XY:
0.0000269
AC XY:
2
AN XY:
74356
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000142
Hom.:
0
Bravo
AF:
0.0000453
ExAC
AF:
0.0000494
AC:
6

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJan 26, 2023The c.361C>T (p.H121Y) alteration is located in exon 2 (coding exon 2) of the LRRC75A gene. This alteration results from a C to T substitution at nucleotide position 361, causing the histidine (H) at amino acid position 121 to be replaced by a tyrosine (Y). 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
Uncertain
0.42
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.26
CADD
Pathogenic
31
DANN
Uncertain
1.0
DEOGEN2
Benign
0.12
.;T
Eigen
Uncertain
0.67
Eigen_PC
Uncertain
0.65
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.94
D;D
M_CAP
Benign
0.027
D
MetaRNN
Uncertain
0.44
T;T
MetaSVM
Benign
-0.65
T
MutationAssessor
Benign
1.9
L;L
PrimateAI
Uncertain
0.69
T
PROVEAN
Uncertain
-3.4
D;D
REVEL
Benign
0.27
Sift
Uncertain
0.0040
D;D
Sift4G
Uncertain
0.012
D;D
Polyphen
1.0
D;D
Vest4
0.67
MutPred
0.28
Gain of catalytic residue at L116 (P = 0.0578);Gain of catalytic residue at L116 (P = 0.0578);
MVP
0.043
MPC
1.3
ClinPred
0.70
D
GERP RS
4.2
Varity_R
0.43
gMVP
0.70

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs768851789; hg19: chr17-16365586; API