17-68600628-C-T

Variant names:

• chr17-68600628-C-T
• rs2907388
• NM_017565.4:c.39G>A

Variant summary

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

The NM_017565.4(FAM20A):​c.39G>A​(p.Leu13Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0398 in 1,560,538 control chromosomes in the GnomAD database, including 2,187 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.040 (189 hom., cov: 32)
  • Exomes 𝑓: 0.040 (1998 hom.)
• Consequence: FAM20A NM_017565.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.76
• Publications: 5 publications found

Genes affected

FAM20A (HGNC:23015): (FAM20A golgi associated secretory pathway pseudokinase) This locus encodes a protein that is likely secreted and may function in hematopoiesis. A mutation at this locus has been associated with amelogenesis imperfecta and gingival hyperplasia syndrome. Alternatively spliced transcript variants have been identified. [provided by RefSeq, Aug 2011]

LINC01482 (HGNC:51128): (long intergenic non-protein coding RNA 1482)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 17-68600628-C-T is Benign according to our data. Variant chr17-68600628-C-T is described in ClinVar as Benign. ClinVar VariationId is 260832.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.76 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017565.4. 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
	FAM20A	NM_017565.4	MANE Select	c.39G>A	p.Leu13Leu	synonymous	Exon 1 of 11	NP_060035.2	Q96MK3
	FAM20A	NM_001243746.2		c.-602G>A		5_prime_UTR	Exon 1 of 12	NP_001230675.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM20A	ENST00000592554.2	TSL:1 MANE Select	c.39G>A	p.Leu13Leu	synonymous	Exon 1 of 11	ENSP00000468308.1	Q96MK3
	FAM20A	ENST00000882126.1		c.39G>A	p.Leu13Leu	synonymous	Exon 1 of 12	ENSP00000552185.1
	FAM20A	ENST00000882123.1		c.39G>A	p.Leu13Leu	synonymous	Exon 1 of 10	ENSP00000552182.1

Frequencies

GnomAD3 genomes AF: 0.0402 AC: 6117 AN: 152126 Hom.: 188 Cov.: 32

Gnomad AFR AF: 0.0447

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0218

Gnomad ASJ AF: 0.0259

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.0394

Gnomad MID AF: 0.0350

Gnomad NFE AF: 0.0294

Gnomad OTH AF: 0.0353

GnomAD2 exomes AF: 0.0525 AC: 8449 AN: 161032 AF XY: 0.0586

Gnomad AFR exome AF: 0.0430

Gnomad AMR exome AF: 0.0122

Gnomad ASJ exome AF: 0.0222

Gnomad EAS exome AF: 0.116

Gnomad FIN exome AF: 0.0348

Gnomad NFE exome AF: 0.0300

Gnomad OTH exome AF: 0.0383

GnomAD4 exome AF: 0.0398 AC: 56044 AN: 1408296 Hom.: 1998 Cov.: 33 AF XY: 0.0426 AC XY: 29695 AN XY: 696574

African (AFR) AF: 0.0443 AC: 1446 AN: 32652

American (AMR) AF: 0.0140 AC: 528 AN: 37674

Ashkenazi Jewish (ASJ) AF: 0.0235 AC: 593 AN: 25272

East Asian (EAS) AF: 0.144 AC: 5420 AN: 37742

South Asian (SAS) AF: 0.144 AC: 11633 AN: 80652

European-Finnish (FIN) AF: 0.0315 AC: 1290 AN: 40912

Middle Eastern (MID) AF: 0.0425 AC: 182 AN: 4278

European-Non Finnish (NFE) AF: 0.0298 AC: 32496 AN: 1090482

Other (OTH) AF: 0.0419 AC: 2456 AN: 58632

GnomAD4 genome AF: 0.0402 AC: 6122 AN: 152242 Hom.: 189 Cov.: 32 AF XY: 0.0432 AC XY: 3213 AN XY: 74428

African (AFR) AF: 0.0447 AC: 1857 AN: 41572

American (AMR) AF: 0.0219 AC: 335 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0259 AC: 90 AN: 3472

East Asian (EAS) AF: 0.112 AC: 573 AN: 5126

South Asian (SAS) AF: 0.156 AC: 751 AN: 4828

European-Finnish (FIN) AF: 0.0394 AC: 418 AN: 10614

Middle Eastern (MID) AF: 0.0377 AC: 11 AN: 292

European-Non Finnish (NFE) AF: 0.0294 AC: 1998 AN: 68002

Other (OTH) AF: 0.0373 AC: 79 AN: 2116

Alfa AF: 0.0308 Hom.: 24

Bravo AF: 0.0372

Asia WGS AF: 0.119 AC: 412 AN: 3476

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	12
DANN	Benign	0.81
PhyloP100		1.8
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: rs2907388; hg19: chr17-66596769; COSMIC: COSV107552751; COSMIC: COSV107552751;