7-193205-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 2P and 17B. PM2 BP4_Strong BP6_Very_Strong BP7 BS1

The NM_020223.4(FAM20C):c.6G>A(p.Lys2=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000698 in 1,458,740 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00043 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00073 (1 hom.)
• Consequence: FAM20C NM_020223.4 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0480

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 -15 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 7-193205-G-A is Benign according to our data. Variant chr7-193205-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 709117.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.048 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000434 (65/149732) while in subpopulation NFE AF= 0.000819 (55/67118). AF 95% confidence interval is 0.000646. There are 0 homozygotes in gnomad4. There are 30 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM20C	NM_020223.4	c.6G>A	p.Lys2=	synonymous_variant	1/10	ENST00000313766.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM20C	ENST00000313766.6	c.6G>A	p.Lys2=	synonymous_variant	1/10	1	NM_020223.4	P1
	ENST00000467050.1	n.233+743C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.000434 AC: 65 AN: 149732 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000146

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000663

Gnomad ASJ AF: 0.000582

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000819

Gnomad OTH AF: 0.000487

GnomAD3 exomes AF: 0.000402 AC: 48 AN: 119260 Hom.: 0 AF XY: 0.000460 AC XY: 30 AN XY: 65236

Gnomad AFR exome AF: 0.000257

Gnomad AMR exome AF: 0.000179

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000831

Gnomad OTH exome AF: 0.00113

GnomAD4 exome AF: 0.000728 AC: 953 AN: 1309008 Hom.: 1 Cov.: 30 AF XY: 0.000713 AC XY: 461 AN XY: 646512

Gnomad4 AFR exome AF: 0.0000756

Gnomad4 AMR exome AF: 0.000247

Gnomad4 ASJ exome AF: 0.000138

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000873

Gnomad4 OTH exome AF: 0.000723

GnomAD4 genome AF: 0.000434 AC: 65 AN: 149732 Hom.: 0 Cov.: 33 AF XY: 0.000411 AC XY: 30 AN XY: 73024

Gnomad4 AFR AF: 0.000146

Gnomad4 AMR AF: 0.0000663

Gnomad4 ASJ AF: 0.000582

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000819

Gnomad4 OTH AF: 0.000487

Alfa AF: 0.000684 Hom.: 0

Bravo AF: 0.000431

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Dec 01, 2023	FAM20C: BP4, BP7 -
Likely benign, criteria provided, single submitter	clinical testing	Invitae	Dec 02, 2023	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
Cadd	Benign	10
Dann	Benign	0.82

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: rs749965678; hg19: chr7-193205;