chr8-16150266-C-T

Position:

chr8-16150266-C-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2

The NM_138715.3(MSR1):c.944G>A(p.Gly315Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000702 in 1,565,984 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 0.0000067 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0000071 ( 0 hom. )

Consequence

MSR1
NM_138715.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.20

Variant links:

Genes affected

MSR1 (HGNC:7376): (macrophage scavenger receptor 1) This gene encodes the class A macrophage scavenger receptors, which include three different types (1, 2, 3) generated by alternative splicing of this gene. These receptors or isoforms are macrophage-specific trimeric integral membrane glycoproteins and have been implicated in many macrophage-associated physiological and pathological processes including atherosclerosis, Alzheimer's disease, and host defense. The isoforms type 1 and type 2 are functional receptors and are able to mediate the endocytosis of modified low density lipoproteins (LDLs). The isoform type 3 does not internalize modified LDL (acetyl-LDL) despite having the domain shown to mediate this function in the types 1 and 2 isoforms. It has an altered intracellular processing and is trapped within the endoplasmic reticulum, making it unable to perform endocytosis. The isoform type 3 can inhibit the function of isoforms type 1 and type 2 when co-expressed, indicating a dominant negative effect and suggesting a mechanism for regulation of scavenger receptor activity in macrophages. [provided by RefSeq, Jul 2008]

MSR1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.799

BS2

High AC in GnomAdExome4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MSR1	NM_138715.3 linkuse as main transcript	c.944G>A	p.Gly315Glu	missense_variant	7/10	ENST00000262101.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MSR1	ENST00000262101.10 linkuse as main transcript	c.944G>A	p.Gly315Glu	missense_variant	7/10	1	NM_138715.3	P1	P21757-1

Frequencies

GnomAD3 genomes

AF:

0.00000666

AC:

AN:

150242

Hom.:

Cov.:

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:

0.000196

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:

0.0000378

AC:

AN:

237866

Hom.:

AF XY:

0.0000387

AC XY:

AN XY:

129256

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000525

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000706

AC:

AN:

1415742

Hom.:

Cov.:

AF XY:

0.00000568

AC XY:

AN XY:

704204

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000210

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.21e-7

Gnomad4 OTH exome

AF:

0.0000173

GnomAD4 genome

AF:

0.00000666

AC:

AN:

150242

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73256

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000196

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000227

ExAC

AF:

0.0000330

AC:

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 submitter

clinical testing

Ambry Genetics

Mar 30, 2024

The c.944G>A (p.G315E) alteration is located in exon 7 (coding exon 6) of the MSR1 gene. This alteration results from a G to A substitution at nucleotide position 944, causing the glycine (G) at amino acid position 315 to be replaced by a glutamic acid (E). 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

Pathogenic

0.87

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Pathogenic

0.29

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.92

.;D;.;.;.;.

Eigen

Pathogenic

0.82

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Uncertain

0.83

LIST_S2

Uncertain

0.90

D;T;D;.;D;D

M_CAP

Uncertain

0.28

MetaRNN

Pathogenic

0.80

D;D;D;D;D;D

MetaSVM

Pathogenic

0.99

MutationAssessor

Pathogenic

4.7

H;H;.;H;.;H

MutationTaster

Benign

0.99

D;D;D;D;D;D

PrimateAI

Uncertain

0.59

PROVEAN

Pathogenic

-7.3

D;D;D;D;D;D

REVEL

Pathogenic

0.76

Sift

Pathogenic

0.0

D;D;D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D;D;D

Polyphen

1.0

D;D;D;D;.;D

Vest4

0.96

MutPred

0.61

.;.;Loss of catalytic residue at S334 (P = 0.0627);.;.;.;

MVP

0.98

MPC

0.012

ClinPred

0.99

GERP RS

4.4

Varity_R

0.97

gMVP

0.73

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over