chr20-38951747-C-T

Variant names:

• chr20-38951747-C-T
• rs1258947449
• NM_030919.3:c.985C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_030919.3(FAM83D):​c.985C>T​(p.Leu329Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: FAM83D NM_030919.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.70
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 20-38951747-C-T is Benign according to our data. Variant chr20-38951747-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2326492.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.7 with no splicing effect.

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.985C>T	p.Leu329Leu	synonymous	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.985C>T	p.Leu329Leu	synonymous	Exon 4 of 4	ENSP00000481465.1	Q9H4H8-1
	FAM83D	ENST00000619304.4	TSL:1	c.1075C>T	p.Leu359Leu	synonymous	Exon 4 of 4	ENSP00000481110.1	A0A087WXK8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000120 AC: 3 AN: 249504 AF XY: 0.0000148

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000330

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461882 Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3 AN XY: 727238

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000671 AC: 3 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112008

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	8.0
DANN	Benign	0.64
PhyloP100		1.7

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: rs1258947449; hg19: chr20-37580390;