chr7-259884-G-T

Variant names:

• chr7-259884-G-T
• rs36170987
• NM_020223.4:c.1659G>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_020223.4(FAM20C):​c.1659G>T​(p.Val553Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.46 in 1,535,618 control chromosomes in the GnomAD database, including 166,710 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.52 (21881 hom., cov: 35)
  • Exomes 𝑓: 0.45 (144829 hom.)
• Consequence: FAM20C NM_020223.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.0870
• Publications: 14 publications found

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]

FAM20C Gene-Disease associations (from GenCC):

• lethal osteosclerotic bone dysplasia

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 7-259884-G-T is Benign according to our data. Variant chr7-259884-G-T is described in ClinVar as Benign. ClinVar VariationId is 193730.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.087 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.689 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020223.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM20C	NM_020223.4	MANE Select	c.1659G>T	p.Val553Val	synonymous	Exon 10 of 10	NP_064608.2	Q8IXL6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM20C	ENST00000313766.6	TSL:1 MANE Select	c.1659G>T	p.Val553Val	synonymous	Exon 10 of 10	ENSP00000322323.5	Q8IXL6-1
	FAM20C	ENST00000515795.1	TSL:1	n.1316G>T		non_coding_transcript_exon	Exon 7 of 7
	FAM20C	ENST00000942064.1		c.1920G>T	p.Val640Val	synonymous	Exon 11 of 11	ENSP00000612123.1

Frequencies

GnomAD3 genomes AF: 0.524 AC: 79666 AN: 152036 Hom.: 21840 Cov.: 35

Gnomad AFR AF: 0.695

Gnomad AMI AF: 0.536

Gnomad AMR AF: 0.375

Gnomad ASJ AF: 0.460

Gnomad EAS AF: 0.507

Gnomad SAS AF: 0.443

Gnomad FIN AF: 0.553

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.511

GnomAD2 exomes AF: 0.438 AC: 61566 AN: 140424 AF XY: 0.439

Gnomad AFR exome AF: 0.703

Gnomad AMR exome AF: 0.254

Gnomad ASJ exome AF: 0.457

Gnomad EAS exome AF: 0.501

Gnomad FIN exome AF: 0.544

Gnomad NFE exome AF: 0.458

Gnomad OTH exome AF: 0.453

GnomAD4 exome AF: 0.453 AC: 626956 AN: 1383464 Hom.: 144829 Cov.: 74 AF XY: 0.452 AC XY: 308680 AN XY: 682612

African (AFR) AF: 0.701 AC: 22129 AN: 31586

American (AMR) AF: 0.272 AC: 9695 AN: 35672

Ashkenazi Jewish (ASJ) AF: 0.461 AC: 11602 AN: 25156

East Asian (EAS) AF: 0.475 AC: 16969 AN: 35702

South Asian (SAS) AF: 0.437 AC: 34628 AN: 79188

European-Finnish (FIN) AF: 0.526 AC: 17978 AN: 34158

Middle Eastern (MID) AF: 0.489 AC: 2775 AN: 5680

European-Non Finnish (NFE) AF: 0.449 AC: 484009 AN: 1078448

Other (OTH) AF: 0.469 AC: 27171 AN: 57874

GnomAD4 genome AF: 0.524 AC: 79759 AN: 152154 Hom.: 21881 Cov.: 35 AF XY: 0.524 AC XY: 38983 AN XY: 74362

African (AFR) AF: 0.696 AC: 28884 AN: 41516

American (AMR) AF: 0.374 AC: 5720 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.460 AC: 1595 AN: 3470

East Asian (EAS) AF: 0.506 AC: 2614 AN: 5164

South Asian (SAS) AF: 0.444 AC: 2141 AN: 4826

European-Finnish (FIN) AF: 0.553 AC: 5865 AN: 10598

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.459 AC: 31202 AN: 67982

Other (OTH) AF: 0.512 AC: 1080 AN: 2108

Alfa AF: 0.466 Hom.: 13794

Bravo AF: 0.517

Asia WGS AF: 0.499 AC: 1733 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	1	Lethal osteosclerotic bone dysplasia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	1.1
DANN	Benign	0.55
PhyloP100		0.087
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs36170987; hg19: chr7-299850; COSMIC: COSV58237859; COSMIC: COSV58237859;