20-38951850-G-A

Variant names:

• chr20-38951850-G-A
• NM_030919.3:c.1088G>A

Variant summary

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

The NM_030919.3(FAM83D):​c.1088G>A​(p.Cys363Tyr) 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. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: FAM83D NM_030919.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.64

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=0.0766395).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM83D	NM_030919.3	c.1088G>A	p.Cys363Tyr	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.1088G>A	p.Cys363Tyr	missense_variant	Exon 4 of 4	1	NM_030919.3	ENSP00000481465.1
FAM83D	ENST00000619304.4	c.1178G>A	p.Cys393Tyr	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

May 20, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1088G>A (p.R363Q) alteration is located in exon 4 (coding exon 4) of the FAM83D gene. This alteration results from a G to A substitution at nucleotide position 1088, causing the arginine (R) at amino acid position 363 to be replaced by a glutamine (Q). 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	0.075
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	3.6
DANN	Benign	0.59
DEOGEN2	Benign	0.0044	.;T
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.38	T;T
M_CAP	Benign	0.0085	T
MetaRNN	Benign	0.077	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.0	.;N
PrimateAI	Benign	0.23	T
Sift4G	Benign	0.55	T;T
Polyphen		0.093	.;B
Vest4		0.21
MutPred		0.23		.;Gain of phosphorylation at C363 (P = 0.0059);
MVP		0.25
ClinPred		0.071	T
GERP RS		4.0
Varity_R		0.054
gMVP		0.19

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: chr20-37580493;