rs13254035

Variant names:

• chr8-143727634-G-A
• rs13254035
• NM_198488.5:c.1827C>T

Your query was ambiguous. Multiple possible variants found:

• chr8-143727634-G-A
• chr8-143727634-G-C

Variant summary

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

The NM_198488.5(FAM83H):​c.1827C>T​(p.Tyr609Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.95 in 1,580,832 control chromosomes in the GnomAD database, including 722,428 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.83 (56385 hom., cov: 33)
  • Exomes 𝑓: 0.96 (666043 hom.)
• Consequence: FAM83H NM_198488.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.315
• Publications: 16 publications found

Genes affected

FAM83H (HGNC:24797): (family with sequence similarity 83 member H) The protein encoded by this gene plays an important role in the structural development and calcification of tooth enamel. Defects in this gene are a cause of amelogenesis imperfecta type 3 (AI3). [provided by RefSeq, Mar 2010]

FAM83H Gene-Disease associations (from GenCC):

• amelogenesis imperfecta, type 3A

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 8-143727634-G-A is Benign according to our data. Variant chr8-143727634-G-A is described in ClinVar as Benign. ClinVar VariationId is 263133.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.315 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM83H	NM_198488.5	c.1827C>T	p.Tyr609Tyr	synonymous_variant	Exon 5 of 5	ENST00000388913.4	NP_940890.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM83H	ENST00000388913.4	c.1827C>T	p.Tyr609Tyr	synonymous_variant	Exon 5 of 5	5	NM_198488.5	ENSP00000373565.3
FAM83H	ENST00000650760.1	c.2430C>T	p.Tyr810Tyr	synonymous_variant	Exon 5 of 5			ENSP00000499217.1
FAM83H	ENST00000395103.2	n.1005C>T		non_coding_transcript_exon_variant	Exon 1 of 2	2		ENSP00000378535.2

Frequencies

GnomAD3 genomes AF: 0.832 AC: 126390 AN: 151942 Hom.: 56383 Cov.: 33

Gnomad AFR AF: 0.471

Gnomad AMI AF: 0.907

Gnomad AMR AF: 0.918

Gnomad ASJ AF: 0.933

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.953

Gnomad FIN AF: 0.994

Gnomad MID AF: 0.892

Gnomad NFE AF: 0.978

Gnomad OTH AF: 0.856

GnomAD2 exomes AF: 0.945 AC: 184387 AN: 195098 AF XY: 0.950

Gnomad AFR exome AF: 0.464

Gnomad AMR exome AF: 0.956

Gnomad ASJ exome AF: 0.936

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 0.995

Gnomad NFE exome AF: 0.978

Gnomad OTH exome AF: 0.946

GnomAD4 exome AF: 0.962 AC: 1374726 AN: 1428782 Hom.: 666043 Cov.: 70 AF XY: 0.963 AC XY: 683560 AN XY: 709768

African (AFR) AF: 0.453 AC: 14545 AN: 32140

American (AMR) AF: 0.952 AC: 40246 AN: 42292

Ashkenazi Jewish (ASJ) AF: 0.933 AC: 23798 AN: 25518

East Asian (EAS) AF: 1.00 AC: 38624 AN: 38632

South Asian (SAS) AF: 0.950 AC: 79479 AN: 83642

European-Finnish (FIN) AF: 0.993 AC: 38923 AN: 39212

Middle Eastern (MID) AF: 0.913 AC: 4714 AN: 5166

European-Non Finnish (NFE) AF: 0.978 AC: 1078730 AN: 1102924

Other (OTH) AF: 0.939 AC: 55667 AN: 59256

GnomAD4 genome AF: 0.831 AC: 126415 AN: 152050 Hom.: 56385 Cov.: 33 AF XY: 0.837 AC XY: 62225 AN XY: 74322

African (AFR) AF: 0.470 AC: 19508 AN: 41464

American (AMR) AF: 0.918 AC: 14038 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.933 AC: 3236 AN: 3470

East Asian (EAS) AF: 1.00 AC: 5097 AN: 5098

South Asian (SAS) AF: 0.953 AC: 4604 AN: 4832

European-Finnish (FIN) AF: 0.994 AC: 10537 AN: 10604

Middle Eastern (MID) AF: 0.884 AC: 258 AN: 292

European-Non Finnish (NFE) AF: 0.978 AC: 66502 AN: 67972

Other (OTH) AF: 0.857 AC: 1810 AN: 2112

Alfa AF: 0.926 Hom.: 27816

Bravo AF: 0.809

Asia WGS AF: 0.943 AC: 3249 AN: 3448

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Amelogenesis imperfecta, hypocalcification type Benign:3

-

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Aug 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 28, 2017

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 11, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.74
DANN	Benign	0.94
PhyloP100		-0.32
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: rs13254035; hg19: chr8-144809804; COSMIC: COSV66353384;