6-112100741-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001033564.3(FAM229B):​c.197C>T​(p.Thr66Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000669 in 1,613,852 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000068 ( 0 hom. )

Consequence

FAM229B
NM_001033564.3 missense

Scores

1
17

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.92
Variant links:
Genes affected
FAM229B (HGNC:33858): (family with sequence similarity 229 member B)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.034916162).
BP6
Variant 6-112100741-C-T is Benign according to our data. Variant chr6-112100741-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2467300.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
FAM229BNM_001033564.3 linkuse as main transcriptc.197C>T p.Thr66Met missense_variant 4/4 ENST00000368656.7 NP_001028736.1 Q4G0N7
FAM229BXM_017011174.3 linkuse as main transcriptc.197C>T p.Thr66Met missense_variant 4/4 XP_016866663.1 Q4G0N7
FAM229BXM_017011175.3 linkuse as main transcriptc.197C>T p.Thr66Met missense_variant 3/3 XP_016866664.1 Q4G0N7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
FAM229BENST00000368656.7 linkuse as main transcriptc.197C>T p.Thr66Met missense_variant 4/41 NM_001033564.3 ENSP00000357645.2 Q4G0N7
FAM229BENST00000604268.1 linkuse as main transcriptc.197C>T p.Thr66Met missense_variant 4/45 ENSP00000474987.1 Q4G0N7

Frequencies

GnomAD3 genomes
AF:
0.0000592
AC:
9
AN:
152136
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
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:
0.000103
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000557
AC:
14
AN:
251372
Hom.:
0
AF XY:
0.0000589
AC XY:
8
AN XY:
135842
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000174
Gnomad ASJ exome
AF:
0.0000992
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000352
Gnomad OTH exome
AF:
0.000326
GnomAD4 exome
AF:
0.0000677
AC:
99
AN:
1461716
Hom.:
0
Cov.:
30
AF XY:
0.0000688
AC XY:
50
AN XY:
727142
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.000268
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000464
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000684
Gnomad4 OTH exome
AF:
0.0000828
GnomAD4 genome
AF:
0.0000592
AC:
9
AN:
152136
Hom.:
0
Cov.:
33
AF XY:
0.0000538
AC XY:
4
AN XY:
74314
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000103
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000920
Hom.:
0
Bravo
AF:
0.0000831
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000494
AC:
6
EpiCase
AF:
0.0000545
EpiControl
AF:
0.0000593

ClinVar

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

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsFeb 16, 2023This 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
AlphaMissense
Benign
0.046
BayesDel_addAF
Benign
-0.38
T
BayesDel_noAF
Benign
-0.49
CADD
Benign
16
DANN
Benign
0.83
DEOGEN2
Benign
0.0020
T;T
Eigen
Benign
-0.53
Eigen_PC
Benign
-0.34
FATHMM_MKL
Benign
0.098
N
LIST_S2
Benign
0.37
.;T
M_CAP
Benign
0.0029
T
MetaRNN
Benign
0.035
T;T
MetaSVM
Benign
-0.95
T
PrimateAI
Uncertain
0.52
T
PROVEAN
Benign
2.9
N;.
REVEL
Benign
0.056
Sift
Benign
1.0
T;.
Sift4G
Benign
0.15
T;T
Polyphen
0.0
B;B
Vest4
0.13
MVP
0.043
MPC
0.26
ClinPred
0.28
T
GERP RS
4.0
Varity_R
0.023
gMVP
0.090

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: rs149743977; hg19: chr6-112421944; API