7-193091-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_020223.4(FAM20C):c.-109C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0924 in 1,015,168 control chromosomes in the GnomAD database, including 4,981 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.065 (419 hom., cov: 33)
  • Exomes 𝑓: 0.097 (4562 hom.)
• Consequence: FAM20C NM_020223.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.02

Genes affected

FAM20C (HGNC:22140): (FAM20C golgi associated secretory pathway kinase) This gene encodes a member of the family of secreted protein kinases. The encoded protein binds calcium and phosphorylates proteins involved in bone mineralization. Mutations in this gene are associated with the autosomal recessive disorder Raine syndrome. [provided by RefSeq, Apr 2014]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 7-193091-C-T is Benign according to our data. Variant chr7-193091-C-T is described in ClinVar as [Benign]. Clinvar id is 1245869.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0964 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM20C	NM_020223.4	c.-109C>T		5_prime_UTR_variant	1/10	ENST00000313766.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM20C	ENST00000313766.6	c.-109C>T		5_prime_UTR_variant	1/10	1	NM_020223.4	P1
	ENST00000467050.1	n.233+857G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0649 AC: 9717 AN: 149662 Hom.: 419 Cov.: 33

Gnomad AFR AF: 0.0189

Gnomad AMI AF: 0.153

Gnomad AMR AF: 0.0518

Gnomad ASJ AF: 0.0355

Gnomad EAS AF: 0.000390

Gnomad SAS AF: 0.0394

Gnomad FIN AF: 0.0985

Gnomad MID AF: 0.0669

Gnomad NFE AF: 0.0984

Gnomad OTH AF: 0.0626

GnomAD4 exome AF: 0.0972 AC: 84135 AN: 865400 Hom.: 4562 Cov.: 11 AF XY: 0.0964 AC XY: 41319 AN XY: 428826

Gnomad4 AFR exome AF: 0.0141

Gnomad4 AMR exome AF: 0.0525

Gnomad4 ASJ exome AF: 0.0321

Gnomad4 EAS exome AF: 0.000165

Gnomad4 SAS exome AF: 0.0434

Gnomad4 FIN exome AF: 0.106

Gnomad4 NFE exome AF: 0.106

Gnomad4 OTH exome AF: 0.0817

GnomAD4 genome AF: 0.0649 AC: 9713 AN: 149768 Hom.: 419 Cov.: 33 AF XY: 0.0642 AC XY: 4693 AN XY: 73120

Gnomad4 AFR AF: 0.0188

Gnomad4 AMR AF: 0.0518

Gnomad4 ASJ AF: 0.0355

Gnomad4 EAS AF: 0.000391

Gnomad4 SAS AF: 0.0394

Gnomad4 FIN AF: 0.0985

Gnomad4 NFE AF: 0.0984

Gnomad4 OTH AF: 0.0619

Alfa AF: 0.0865 Hom.: 79

Bravo AF: 0.0607

Asia WGS AF: 0.0140 AC: 47 AN: 3314

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
Cadd	Benign	9.7
Dann	Benign	0.96
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Other links and lift over

dbSNP: rs116903250; hg19: chr7-193091; COSMIC: COSV58237300; COSMIC: COSV58237300;