chr1-20553617-G-T

Variant names:

• chr1-20553617-G-T
• NM_207334.3:c.644G>T

Variant summary

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

The NM_207334.3(FAM43B):​c.644G>T​(p.Arg215Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FAM43B NM_207334.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.32

Genes affected

FAM43B (HGNC:31791): (family with sequence similarity 43 member B)

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM43B	NM_207334.3	c.644G>T	p.Arg215Leu	missense_variant	Exon 1 of 1	ENST00000332947.6	NP_997217.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM43B	ENST00000332947.6	c.644G>T	p.Arg215Leu	missense_variant	Exon 1 of 1	6	NM_207334.3	ENSP00000331397.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1126188 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 543286

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

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 08, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.644G>T (p.R215L) alteration is located in exon 1 (coding exon 1) of the FAM43B gene. This alteration results from a G to T substitution at nucleotide position 644, causing the arginine (R) at amino acid position 215 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	Pathogenic	0.67
BayesDel_addAF	Uncertain	0.018	T
BayesDel_noAF	Benign	-0.21
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Benign	0.019	T
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.94	D
M_CAP	Pathogenic	0.82	D
MetaRNN	Uncertain	0.47	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.5	M
PrimateAI	Pathogenic	0.97	D
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.21
Sift	Uncertain	0.0070	D
Sift4G	Benign	0.12	T
Polyphen		0.97	D
Vest4		0.40
MutPred		0.49		Loss of MoRF binding (P = 0.094);
MVP		0.37
ClinPred		0.95	D
GERP RS		3.4
Varity_R		0.31
gMVP		0.54

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: chr1-20880110;