4-2663244-G-A

Position:

• chr4-2663244-G-A

Variant summary

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

The NM_001366318.2(FAM193A):​c.2035G>A​(p.Glu679Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000411 in 1,461,086 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: FAM193A NM_001366318.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.06

Genes affected

FAM193A (HGNC:16822): (family with sequence similarity 193 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=0.14722857).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM193A	NM_001366318.2	c.2035G>A	p.Glu679Lys	missense_variant	12/21	ENST00000637812.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM193A	ENST00000637812.2	c.2035G>A	p.Glu679Lys	missense_variant	12/21	5	NM_001366318.2	A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1461086 Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3 AN XY: 726852

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: 0.00000540

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 01, 2024

The c.1162G>A (p.E388K) alteration is located in exon 10 (coding exon 8) of the FAM193A gene. This alteration results from a G to A substitution at nucleotide position 1162, causing the glutamic acid (E) at amino acid position 388 to be replaced by a lysine (K). 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	0.094
BayesDel_addAF	Benign	-0.079	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0055	.;.;.;T;.;.;T
Eigen	Benign	0.10
Eigen_PC	Benign	0.16
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D;D;D;D;D;.;D
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.15	T;T;T;T;T;T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	0.81	.;L;L;L;.;L;.
MutationTaster	Benign	0.96	D;D;D;D;D
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.3	.;N;N;N;N;N;N
REVEL	Benign	0.15
Sift	Uncertain	0.014	.;D;D;D;D;D;D
Sift4G	Benign	0.62	.;T;T;T;T;T;T
Polyphen		0.13, 0.28	.;.;B;B;.;.;.
Vest4		0.50, 0.51, 0.54, 0.53, 0.57
MutPred		0.12		.;Gain of glycosylation at S383 (P = 0.0047);Gain of glycosylation at S383 (P = 0.0047);Gain of glycosylation at S383 (P = 0.0047);.;Gain of glycosylation at S383 (P = 0.0047);.;
MVP		0.043
MPC		0.26
ClinPred		0.54	D
GERP RS		5.3
Varity_R		0.13
gMVP		0.25

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: chr4-2664971; COSMIC: COSV105909299; COSMIC: COSV105909299;