20-38951843-C-T

Variant names:

• chr20-38951843-C-T
• NM_030919.3:c.1081C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_030919.3(FAM83D):​c.1081C>T​(p.His361Tyr) 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. 14/19 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: 0.0380
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08669135).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030919.3. 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
	FAM83D	NM_030919.3	MANE Select	c.1081C>T	p.His361Tyr	missense	Exon 4 of 4	NP_112181.3	Q9H4H8-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM83D	ENST00000619850.2	TSL:1 MANE Select	c.1081C>T	p.His361Tyr	missense	Exon 4 of 4	ENSP00000481465.1	Q9H4H8-1
	FAM83D	ENST00000619304.4	TSL:1	c.1171C>T	p.His391Tyr	missense	Exon 4 of 4	ENSP00000481110.1	A0A087WXK8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.27
DANN	Benign	0.27
DEOGEN2	Benign	0.00097	T
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.33	T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.087	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.97	L
PhyloP100		0.038
PrimateAI	Benign	0.23	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.15
MutPred		0.24		Gain of phosphorylation at H361 (P = 0.0128)
MVP		0.30
ClinPred		0.034	T
GERP RS		2.5
Varity_R		0.035
gMVP		0.089
Mutation Taster		=78/22	polymorphism

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

hg19: chr20-37580486;