chr6-4068802-C-T

Variant summary

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

The NM_173563.3(FAM217A):​c.1421G>A​(p.Arg474Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,814 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

FAM217A
NM_173563.3 missense

Scores

1
18

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.115
Variant links:
Genes affected
FAM217A (HGNC:21362): (family with sequence similarity 217 member A)

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=0.044210345).
BP6
Variant 6-4068802-C-T is Benign according to our data. Variant chr6-4068802-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2309752.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FAM217ANM_173563.3 linkc.1421G>A p.Arg474Gln missense_variant Exon 7 of 7 ENST00000274673.8 NP_775834.2 Q8IXS0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FAM217AENST00000274673.8 linkc.1421G>A p.Arg474Gln missense_variant Exon 7 of 7 1 NM_173563.3 ENSP00000274673.3 Q8IXS0
FAM217AENST00000639338.1 linkc.1823G>A p.Arg608Gln missense_variant Exon 9 of 9 5 ENSP00000492773.1 A0A1W2PRP4
FAM217AENST00000380188.2 linkn.1830G>A non_coding_transcript_exon_variant Exon 5 of 5 2
FAM217AENST00000469157.5 linkn.391+4473G>A intron_variant Intron 2 of 2 5

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251330
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135836
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.00
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:
0.00
GnomAD4 exome
AF:
0.00000410
AC:
6
AN:
1461814
Hom.:
0
Cov.:
30
AF XY:
0.00000413
AC XY:
3
AN XY:
727204
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.00000360
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000756
ExAC
AF:
0.00000824
AC:
1

ClinVar

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

Submissions by phenotype

not specified Benign:1
Aug 30, 2022
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
AlphaMissense
Benign
0.086
BayesDel_addAF
Benign
-0.48
T
BayesDel_noAF
Benign
-0.75
CADD
Benign
11
DANN
Uncertain
0.98
DEOGEN2
Benign
0.0056
T;.
Eigen
Benign
-0.86
Eigen_PC
Benign
-0.84
FATHMM_MKL
Benign
0.060
N
LIST_S2
Benign
0.67
T;T
M_CAP
Benign
0.0034
T
MetaRNN
Benign
0.044
T;T
MetaSVM
Benign
-0.95
T
MutationAssessor
Benign
0.63
N;.
PrimateAI
Benign
0.19
T
PROVEAN
Benign
-1.4
N;.
REVEL
Benign
0.041
Sift
Benign
0.27
T;.
Sift4G
Benign
0.19
T;.
Polyphen
0.17
B;.
Vest4
0.080
MutPred
0.32
Loss of MoRF binding (P = 0.0186);.;
MVP
0.16
MPC
0.040
ClinPred
0.057
T
GERP RS
0.16
Varity_R
0.049
gMVP
0.046

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: rs754475677; hg19: chr6-4069036; COSMIC: COSV51158954; COSMIC: COSV51158954; API