17-16443809-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001113567.3(LRRC75A):​c.814G>A​(p.Val272Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000297 in 1,613,774 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000031 ( 0 hom. )

Consequence

LRRC75A
NM_001113567.3 missense

Scores

5
7
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.48
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 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.772

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LRRC75ANM_001113567.3 linkc.814G>A p.Val272Met missense_variant Exon 4 of 4 ENST00000470794.2 NP_001107039.1 Q8NAA5-1B7ZMA3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LRRC75AENST00000470794.2 linkc.814G>A p.Val272Met missense_variant Exon 4 of 4 1 NM_001113567.3 ENSP00000419502.1 Q8NAA5-1

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152232
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000159
AC:
4
AN:
251158
Hom.:
0
AF XY:
0.00000737
AC XY:
1
AN XY:
135722
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
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:
0.0000264
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000308
AC:
45
AN:
1461542
Hom.:
0
Cov.:
33
AF XY:
0.0000248
AC XY:
18
AN XY:
727016
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
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:
0.0000387
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152232
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74384
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000116
Hom.:
0
Bravo
AF:
0.0000302
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.00
AC:
0
ExAC
AF:
0.0000247
AC:
3
EpiCase
AF:
0.000109
EpiControl
AF:
0.00

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jul 25, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.814G>A (p.V272M) alteration is located in exon 4 (coding exon 4) of the LRRC75A gene. This alteration results from a G to A substitution at nucleotide position 814, causing the valine (V) at amino acid position 272 to be replaced by a methionine (M). 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
0.32
BayesDel_addAF
Uncertain
0.088
D
BayesDel_noAF
Uncertain
-0.030
CADD
Pathogenic
31
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.18
T
Eigen
Pathogenic
0.75
Eigen_PC
Pathogenic
0.75
FATHMM_MKL
Uncertain
0.84
D
LIST_S2
Uncertain
0.96
D
M_CAP
Benign
0.022
T
MetaRNN
Pathogenic
0.77
D
MetaSVM
Benign
-0.64
T
MutationAssessor
Uncertain
2.1
M
PrimateAI
Pathogenic
0.85
D
PROVEAN
Benign
-2.3
N
REVEL
Benign
0.26
Sift
Uncertain
0.0050
D
Sift4G
Uncertain
0.0050
D
Polyphen
1.0
D
Vest4
0.85
MVP
0.16
MPC
1.3
ClinPred
0.81
D
GERP RS
5.3
Varity_R
0.20
gMVP
0.53

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: rs775774729; hg19: chr17-16347123; API