X-34942922-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_152631.3(FAM47B):​c.91G>T​(p.Ala31Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 24)

Consequence

FAM47B
NM_152631.3 missense

Scores

17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.703
Variant links:
Genes affected
FAM47B (HGNC:26659): (family with sequence similarity 47 member B)

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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=0.06330943).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FAM47BNM_152631.3 linkc.91G>T p.Ala31Ser missense_variant Exon 1 of 1 ENST00000329357.6 NP_689844.2 Q8NA70

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FAM47BENST00000329357.6 linkc.91G>T p.Ala31Ser missense_variant Exon 1 of 1 6 NM_152631.3 ENSP00000328307.5 Q8NA70

Frequencies

GnomAD3 genomes
Cov.:
24
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
24

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 30, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.91G>T (p.A31S) alteration is located in exon 1 (coding exon 1) of the FAM47B gene. This alteration results from a G to T substitution at nucleotide position 91, causing the alanine (A) at amino acid position 31 to be replaced by a serine (S). 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
0.14
BayesDel_addAF
Benign
-0.50
T
BayesDel_noAF
Benign
-0.96
CADD
Benign
0.28
DANN
Benign
0.39
DEOGEN2
Benign
0.0089
T
FATHMM_MKL
Benign
0.0042
N
LIST_S2
Benign
0.60
T
M_CAP
Benign
0.0015
T
MetaRNN
Benign
0.063
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.7
L
PrimateAI
Benign
0.39
T
PROVEAN
Benign
-1.9
N
REVEL
Benign
0.027
Sift
Benign
0.20
T
Sift4G
Benign
0.17
T
Polyphen
0.26
B
Vest4
0.054
MutPred
0.23
Gain of phosphorylation at A31 (P = 0.0227);
MVP
0.45
MPC
0.24
ClinPred
0.084
T
GERP RS
-1.7
Varity_R
0.16
gMVP
0.023

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-34961039; API