chr11-65573441-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_001098784.2(FAM89B):​c.380C>T​(p.Pro127Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,088 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

FAM89B
NM_001098784.2 missense

Scores

1
5
9

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.77
Variant links:
Genes affected
FAM89B (HGNC:16708): (family with sequence similarity 89 member B) Predicted to enable transcription corepressor binding activity. Predicted to be involved in establishment of cell polarity; negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway; and positive regulation of cell migration. Predicted to be active in cytoplasm and lamellipodium. [provided by Alliance of Genome Resources, Apr 2022]
ZNRD2 (HGNC:11328): (zinc ribbon domain containing 2) This antigen is recognized by a subset of anti-centromere antibodies from patients with scleroderma and/or Sjogren's syndrome. Subcellular localization has not yet been established. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.103114694).
BP6
Variant 11-65573441-C-T is Benign according to our data. Variant chr11-65573441-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3512535.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FAM89BNM_001098785.2 linkc.370C>T p.Leu124Leu synonymous_variant Exon 2 of 2 ENST00000530349.2 NP_001092255.1 Q8N5H3-3
FAM89BNM_001098784.2 linkc.380C>T p.Pro127Leu missense_variant Exon 2 of 2 NP_001092254.1 Q8N5H3-4
FAM89BNM_152832.3 linkc.331C>T p.Leu111Leu synonymous_variant Exon 2 of 2 NP_690045.1 Q8N5H3-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FAM89BENST00000449319.2 linkc.380C>T p.Pro127Leu missense_variant Exon 2 of 2 1 ENSP00000402439.2 Q8N5H3-4
FAM89BENST00000530349.2 linkc.370C>T p.Leu124Leu synonymous_variant Exon 2 of 2 2 NM_001098785.2 ENSP00000431459.1 Q8N5H3-3
FAM89BENST00000316409.2 linkc.331C>T p.Leu111Leu synonymous_variant Exon 2 of 2 1 ENSP00000314829.2 Q8N5H3-1
ZNRD2ENST00000526433.1 linkc.236C>T p.Pro79Leu missense_variant Exon 3 of 3 3 ENSP00000435982.1 H0YEK1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461088
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
726802
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.00e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Sep 10, 2024
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.18
D
BayesDel_noAF
Uncertain
0.020
CADD
Benign
14
DANN
Uncertain
1.0
Eigen
Benign
-0.054
Eigen_PC
Benign
0.049
FATHMM_MKL
Uncertain
0.82
D
LIST_S2
Benign
0.40
T
M_CAP
Benign
0.026
D
MetaRNN
Benign
0.10
T
MetaSVM
Benign
-1.0
T
PROVEAN
Benign
0.79
N
REVEL
Benign
0.17
Sift
Uncertain
0.0070
D
Sift4G
Uncertain
0.012
D
Vest4
0.17
MutPred
0.27
Gain of sheet (P = 0.0061);
MVP
0.081
ClinPred
0.92
D
GERP RS
4.4

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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: chr11-65340912; API