chr3-194687583-A-C

Variant names:

• chr3-194687583-A-C
• NM_153690.5:c.757A>C

Variant summary

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

The NM_153690.5(FAM43A):​c.757A>C​(p.Ile253Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: FAM43A NM_153690.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.80

Genes affected

FAM43A (HGNC:26888): (family with sequence similarity 43 member A)

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=0.23217216).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM43A	NM_153690.5	c.757A>C	p.Ile253Leu	missense_variant	Exon 1 of 1	ENST00000329759.6	NP_710157.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM43A	ENST00000329759.6	c.757A>C	p.Ile253Leu	missense_variant	Exon 1 of 1	6	NM_153690.5	ENSP00000371397.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 17, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.757A>C (p.I253L) alteration is located in exon 1 (coding exon 1) of the FAM43A gene. This alteration results from a A to C substitution at nucleotide position 757, causing the isoleucine (I) at amino acid position 253 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	0.87
BayesDel_addAF	Uncertain	0.085	D
BayesDel_noAF	Benign	-0.12
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.25	T
Eigen	Benign	-0.072
Eigen_PC	Benign	0.052
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.057	D
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.42	T
MutationAssessor	Uncertain	2.5	M
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-1.8	N
REVEL	Uncertain	0.35
Sift	Uncertain	0.0040	D
Sift4G	Benign	0.30	T
Polyphen		0.0090	B
Vest4		0.42
MutPred		0.41		Loss of catalytic residue at L258 (P = 0.0265);
MVP		0.51
ClinPred		0.92	D
GERP RS		2.7
Varity_R		0.37
gMVP		0.32

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: chr3-194408312;