20-38952261-C-T

Variant names:

• chr20-38952261-C-T
• NM_030919.3:c.1499C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_030919.3(FAM83D):​c.1499C>T​(p.Thr500Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: FAM83D NM_030919.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.45

Genes affected

FAM83D (HGNC:16122): (family with sequence similarity 83 member D) Enables kinesin binding activity; microtubule binding activity; and protein kinase binding activity. Involved in several processes, including positive regulation of cell cycle G1/S phase transition; protein localization to mitotic spindle; and regulation of intracellular signal transduction. Located in cytosol; intercellular bridge; and mitotic spindle pole. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10998395).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM83D	NM_030919.3	c.1499C>T	p.Thr500Ile	missense_variant	Exon 4 of 4	ENST00000619850.2	NP_112181.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM83D	ENST00000619850.2	c.1499C>T	p.Thr500Ile	missense_variant	Exon 4 of 4	1	NM_030919.3	ENSP00000481465.1
FAM83D	ENST00000619304.4	c.1589C>T	p.Thr530Ile	missense_variant	Exon 4 of 4	1		ENSP00000481110.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 01, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1499C>T (p.S500L) alteration is located in exon 4 (coding exon 4) of the FAM83D gene. This alteration results from a C to T substitution at nucleotide position 1499, causing the serine (S) at amino acid position 500 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	8.3
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0027	.;T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.46	T;T
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	.;L
PrimateAI	Benign	0.35	T
Sift4G	Benign	0.17	T;T
Polyphen		0.18	.;B
Vest4		0.18
MutPred		0.18		.;Loss of glycosylation at T500 (P = 0.0216);
MVP		0.21
ClinPred		0.24	T
GERP RS		5.0
Varity_R		0.036
gMVP		0.15

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-37580904;