7-193245-G-T

Position:

• chr7-193245-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_020223.4(FAM20C):​c.46G>T​(p.Val16Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00199 in 1,466,390 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.011 (26 hom., cov: 33)
  • Exomes 𝑓: 0.00094 (20 hom.)
• Consequence: FAM20C NM_020223.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 3.00

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003346026).
• BP6: Variant 7-193245-G-T is Benign according to our data. Variant chr7-193245-G-T is described in ClinVar as [Benign]. Clinvar id is 193426.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-193245-G-T is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0111 (1670/150092) while in subpopulation AFR AF= 0.0385 (1593/41344). AF 95% confidence interval is 0.037. There are 26 homozygotes in gnomad4. There are 768 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 26 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM20C	NM_020223.4	c.46G>T	p.Val16Leu	missense_variant	1/10	ENST00000313766.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM20C	ENST00000313766.6	c.46G>T	p.Val16Leu	missense_variant	1/10	1	NM_020223.4	P1
	ENST00000467050.1	n.233+703C>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0111 AC: 1672 AN: 149984 Hom.: 27 Cov.: 33

Gnomad AFR AF: 0.0387

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00318

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: 0.000178

Gnomad OTH AF: 0.00776

GnomAD3 exomes AF: 0.00148 AC: 172 AN: 116294 Hom.: 6 AF XY: 0.00112 AC XY: 71 AN XY: 63670

Gnomad AFR exome AF: 0.0368

Gnomad AMR exome AF: 0.00137

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: 0.0000656

Gnomad OTH exome AF: 0.000868

GnomAD4 exome AF: 0.000943 AC: 1241 AN: 1316298 Hom.: 20 Cov.: 30 AF XY: 0.000808 AC XY: 525 AN XY: 649842

Gnomad4 AFR exome AF: 0.0394

Gnomad4 AMR exome AF: 0.00143

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000781

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000250

Gnomad4 OTH exome AF: 0.00210

GnomAD4 genome AF: 0.0111 AC: 1670 AN: 150092 Hom.: 26 Cov.: 33 AF XY: 0.0105 AC XY: 768 AN XY: 73292

Gnomad4 AFR AF: 0.0385

Gnomad4 AMR AF: 0.00318

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000179

Gnomad4 OTH AF: 0.00768

Alfa AF: 0.00158 Hom.: 3

ESP6500AA AF: 0.0332 AC: 93

ESP6500EA AF: 0.000191 AC: 1

ExAC AF: 0.00340 AC: 74

Asia WGS AF: 0.00250 AC: 8 AN: 3212

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Oct 28, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 24, 2024	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Feb 26, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0046	T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.16
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.79	T
MetaRNN	Benign	0.0033	T
MetaSVM	Benign	-0.62	T
MutationTaster	Benign	1.0	D
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-0.75	N
REVEL	Benign	0.19
Sift	Benign	0.16	T
Sift4G	Benign	0.22	T
Polyphen		0.0020	B
Vest4		0.17
MutPred		0.35		Loss of MoRF binding (P = 0.0982);
MVP		0.37
MPC		0.47
ClinPred		0.0071	T
GERP RS		2.9
Varity_R		0.16
gMVP		0.66

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: rs150401144; hg19: chr7-193245;