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GeneBe

14-51720077-T-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001267046.2(FRMD6):c.1047T>C(p.Ser349=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00195 in 1,613,096 control chromosomes in the GnomAD database, including 47 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.010 ( 22 hom., cov: 32)
Exomes 𝑓: 0.0011 ( 25 hom. )

Consequence

FRMD6
NM_001267046.2 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.54
Variant links:
Genes affected
FRMD6 (HGNC:19839): (FERM domain containing 6) Predicted to be involved in actomyosin structure organization. Predicted to act upstream of or within apical constriction; cellular protein localization; and regulation of actin filament-based process. Predicted to be located in apical junction complex. Predicted to be active in cytoskeleton. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.74).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 14-51720077-T-C is Benign according to our data. Variant chr14-51720077-T-C is described in ClinVar as [Benign]. Clinvar id is 776839.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-3.54 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0104 (1577/152270) while in subpopulation AFR AF= 0.0359 (1493/41538). AF 95% confidence interval is 0.0344. There are 22 homozygotes in gnomad4. There are 734 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 22 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
FRMD6NM_001267046.2 linkuse as main transcriptc.1047T>C p.Ser349= synonymous_variant 11/14 ENST00000344768.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
FRMD6ENST00000344768.10 linkuse as main transcriptc.1047T>C p.Ser349= synonymous_variant 11/142 NM_001267046.2 Q96NE9-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0103
AC:
1566
AN:
152152
Hom.:
22
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0358
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00445
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00574
GnomAD3 exomes
AF:
0.00258
AC:
631
AN:
244562
Hom.:
4
AF XY:
0.00177
AC XY:
235
AN XY:
132606
show subpopulations
Gnomad AFR exome
AF:
0.0349
Gnomad AMR exome
AF:
0.00137
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000985
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000833
Gnomad OTH exome
AF:
0.00284
GnomAD4 exome
AF:
0.00107
AC:
1570
AN:
1460826
Hom.:
25
Cov.:
29
AF XY:
0.000962
AC XY:
699
AN XY:
726580
show subpopulations
Gnomad4 AFR exome
AF:
0.0379
Gnomad4 AMR exome
AF:
0.00159
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000459
Gnomad4 OTH exome
AF:
0.00267
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0104
AC:
1577
AN:
152270
Hom.:
22
Cov.:
32
AF XY:
0.00986
AC XY:
734
AN XY:
74464
show subpopulations
Gnomad4 AFR
AF:
0.0359
Gnomad4 AMR
AF:
0.00445
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00568
Alfa
AF:
0.00199
Hom.:
9
Bravo
AF:
0.0116
Asia WGS
AF:
0.00318
AC:
11
AN:
3478
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

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

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeMay 09, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.74
Cadd
Benign
3.1
Dann
Benign
0.61

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs111643867; hg19: chr14-52186795; API