10-49131896-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001164484.2(FAM170B):​c.569T>C​(p.Leu190Pro) 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. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

FAM170B
NM_001164484.2 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.08
Variant links:
Genes affected
FAM170B (HGNC:19736): (family with sequence similarity 170 member B) Predicted to be involved in fertilization; positive regulation of acrosome reaction; and regulation of fertilization. Located in acrosomal vesicle. [provided by Alliance of Genome Resources, Apr 2022]
FAM170B-AS1 (HGNC:45006): (FAM170B antisense RNA 1)

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.09540403).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FAM170BNM_001164484.2 linkc.569T>C p.Leu190Pro missense_variant Exon 2 of 2 ENST00000311787.6 NP_001157956.1 A6NMN3
FAM170B-AS1NR_038973.1 linkn.439-3760A>G intron_variant Intron 1 of 5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FAM170BENST00000311787.6 linkc.569T>C p.Leu190Pro missense_variant Exon 2 of 2 1 NM_001164484.2 ENSP00000308292.6 A6NMN3
FAM170B-AS1ENST00000435809.1 linkn.192-3981A>G intron_variant Intron 1 of 2 3
FAM170B-AS1ENST00000442525.5 linkn.439-3760A>G intron_variant Intron 1 of 5 2
FAM170B-AS1ENST00000443389.5 linkn.434-9357A>G intron_variant Intron 1 of 5 5

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
86
GnomAD4 genome
Cov.:
33

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Apr 01, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.569T>C (p.L190P) alteration is located in exon 2 (coding exon 2) of the FAM170B gene. This alteration results from a T to C substitution at nucleotide position 569, causing the leucine (L) at amino acid position 190 to be replaced by a proline (P). 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
0.11
BayesDel_addAF
Benign
-0.085
T
BayesDel_noAF
Benign
-0.36
CADD
Benign
12
DANN
Benign
0.95
DEOGEN2
Benign
0.0010
T
Eigen
Benign
-0.37
Eigen_PC
Benign
-0.34
FATHMM_MKL
Benign
0.12
N
LIST_S2
Benign
0.31
T
M_CAP
Benign
0.029
D
MetaRNN
Benign
0.095
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.9
L
PrimateAI
Benign
0.47
T
PROVEAN
Benign
0.32
N
REVEL
Benign
0.20
Sift
Benign
0.21
T
Sift4G
Benign
0.31
T
Polyphen
0.20
B
Vest4
0.24
MutPred
0.47
Gain of loop (P = 0.0079);
MVP
0.49
ClinPred
0.38
T
GERP RS
4.6
Varity_R
0.18
gMVP
0.46

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: chr10-50339941; API