rs35933858

Variant summary

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

The NM_025074.7(FRAS1):ā€‹c.10153T>Cā€‹(p.Tyr3385His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,382 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/15 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y3385D) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

FRAS1
NM_025074.7 missense

Scores

13

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.79
Variant links:
Genes affected
FRAS1 (HGNC:19185): (Fraser extracellular matrix complex subunit 1) This gene encodes an extracellular matrix protein that appears to function in the regulation of epidermal-basement membrane adhesion and organogenesis during development. Mutations in this gene cause Fraser syndrome, a multisystem malformation that can include craniofacial, urogenital and respiratory system abnormalities. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]

Genome browser will be placed here

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=0.079046994).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
FRAS1NM_025074.7 linkuse as main transcriptc.10153T>C p.Tyr3385His missense_variant 65/74 ENST00000512123.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
FRAS1ENST00000512123.4 linkuse as main transcriptc.10153T>C p.Tyr3385His missense_variant 65/745 NM_025074.7 P1Q86XX4-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000402
AC:
1
AN:
248652
Hom.:
0
AF XY:
0.00000741
AC XY:
1
AN XY:
134898
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461382
Hom.:
0
Cov.:
33
AF XY:
0.00000138
AC XY:
1
AN XY:
726998
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:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.27
T
BayesDel_noAF
Benign
-0.53
CADD
Benign
14
DANN
Benign
0.97
Eigen
Benign
-0.68
Eigen_PC
Benign
-0.51
FATHMM_MKL
Benign
0.19
N
LIST_S2
Benign
0.61
T
M_CAP
Benign
0.0017
T
MetaRNN
Benign
0.079
T
MetaSVM
Benign
-1.0
T
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.23
T
Sift4G
Benign
0.18
T
Vest4
0.25
MVP
0.45
ClinPred
0.039
T
GERP RS
3.6
gMVP
0.28

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: rs35933858; hg19: chr4-79434685; API