rs11136321

Variant names:

• chr8-143726577-G-A
• rs11136321
• NM_198488.5:c.2884C>T

Your query was ambiguous. Multiple possible variants found:

• chr8-143726577-G-A
• chr8-143726577-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.2884C>T​(p.Leu962Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.732 in 1,602,914 control chromosomes in the GnomAD database, including 441,022 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.61 (31687 hom., cov: 33)
  • Exomes 𝑓: 0.74 (409335 hom.)
• Consequence: FAM83H NM_198488.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.279
• 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=-0.63).
• BP6: Variant 8-143726577-G-A is Benign according to our data. Variant chr8-143726577-G-A is described in ClinVar as Benign. ClinVar VariationId is 263135.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.279 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.766 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM83H	NM_198488.5	c.2884C>T	p.Leu962Leu	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.2884C>T	p.Leu962Leu	synonymous_variant	Exon 5 of 5	5	NM_198488.5	ENSP00000373565.3
FAM83H	ENST00000650760.1	c.3487C>T	p.Leu1163Leu	synonymous_variant	Exon 5 of 5			ENSP00000499217.1
FAM83H	ENST00000395103.2	n.2062C>T		non_coding_transcript_exon_variant	Exon 1 of 2	2		ENSP00000378535.2

Frequencies

GnomAD3 genomes AF: 0.611 AC: 92877 AN: 151908 Hom.: 31696 Cov.: 33

Gnomad AFR AF: 0.291

Gnomad AMI AF: 0.822

Gnomad AMR AF: 0.677

Gnomad ASJ AF: 0.702

Gnomad EAS AF: 0.449

Gnomad SAS AF: 0.684

Gnomad FIN AF: 0.737

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.771

Gnomad OTH AF: 0.634

GnomAD2 exomes AF: 0.677 AC: 155710 AN: 229990 AF XY: 0.688

Gnomad AFR exome AF: 0.272

Gnomad AMR exome AF: 0.643

Gnomad ASJ exome AF: 0.700

Gnomad EAS exome AF: 0.433

Gnomad FIN exome AF: 0.729

Gnomad NFE exome AF: 0.767

Gnomad OTH exome AF: 0.696

GnomAD4 exome AF: 0.744 AC: 1079900 AN: 1450890 Hom.: 409335 Cov.: 85 AF XY: 0.743 AC XY: 536843 AN XY: 722156

African (AFR) AF: 0.268 AC: 8958 AN: 33452

American (AMR) AF: 0.648 AC: 28896 AN: 44570

Ashkenazi Jewish (ASJ) AF: 0.705 AC: 18384 AN: 26088

East Asian (EAS) AF: 0.468 AC: 18567 AN: 39666

South Asian (SAS) AF: 0.695 AC: 59879 AN: 86170

European-Finnish (FIN) AF: 0.734 AC: 31955 AN: 43526

Middle Eastern (MID) AF: 0.628 AC: 3618 AN: 5762

European-Non Finnish (NFE) AF: 0.780 AC: 867166 AN: 1111394

Other (OTH) AF: 0.705 AC: 42477 AN: 60262

GnomAD4 genome AF: 0.611 AC: 92881 AN: 152024 Hom.: 31687 Cov.: 33 AF XY: 0.611 AC XY: 45379 AN XY: 74322

African (AFR) AF: 0.290 AC: 12046 AN: 41478

American (AMR) AF: 0.677 AC: 10358 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.702 AC: 2437 AN: 3470

East Asian (EAS) AF: 0.449 AC: 2298 AN: 5120

South Asian (SAS) AF: 0.684 AC: 3298 AN: 4824

European-Finnish (FIN) AF: 0.737 AC: 7815 AN: 10600

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.771 AC: 52382 AN: 67924

Other (OTH) AF: 0.630 AC: 1326 AN: 2106

Alfa AF: 0.694 Hom.: 19128

Bravo AF: 0.588

EpiCase AF: 0.756

EpiControl AF: 0.764

ClinVar

Significance: Benign

Submissions summary: Benign:5

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

- -

Jul 28, 2017

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 10, 2021

Genome-Nilou Lab

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

- -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	3.6
DANN	Benign	0.87
PhyloP100		0.28
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: rs11136321; hg19: chr8-144808747; COSMIC: COSV62027720; COSMIC: COSV62027720;