17-49711262-A-G

Variant names:

• chr17-49711262-A-G
• NM_030802.4:c.1355T>C

Variant summary

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

The NM_030802.4(FAM117A):​c.1355T>C​(p.Met452Thr) 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. 14/20 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)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FAM117A NM_030802.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.37

Genes affected

FAM117A (HGNC:24179): (family with sequence similarity 117 member A)

ENSG00000250751 (HGNC:):

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=0.15760282).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM117A	NM_030802.4	c.1355T>C	p.Met452Thr	missense_variant	Exon 8 of 8	ENST00000240364.7	NP_110429.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM117A	ENST00000240364.7	c.1355T>C	p.Met452Thr	missense_variant	Exon 8 of 8	1	NM_030802.4	ENSP00000240364.2
FAM117A	ENST00000513602.5	c.539T>C	p.Met180Thr	missense_variant	Exon 8 of 8	2		ENSP00000465808.1
ENSG00000250751	ENST00000512720.1	n.142+2787A>G		intron_variant	Intron 1 of 1	3
FAM117A	ENST00000503573.5	n.*691T>C		downstream_gene_variant		5		ENSP00000467070.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1449948 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 719696

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

Jan 24, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1355T>C (p.M452T) alteration is located in exon 8 (coding exon 8) of the FAM117A gene. This alteration results from a T to C substitution at nucleotide position 1355, causing the methionine (M) at amino acid position 452 to be replaced by a threonine (T). 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	0.19
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	22
DANN	Benign	0.97
DEOGEN2	Benign	0.022	T;.
Eigen	Benign	-0.14
Eigen_PC	Benign	0.079
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.64	T;T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;.
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-1.0	N;.
REVEL	Benign	0.060
Sift	Uncertain	0.015	D;.
Sift4G	Uncertain	0.050	T;D
Polyphen		0.0	B;.
Vest4		0.17
MutPred		0.13		Loss of stability (P = 0.0517);.;
MVP		0.088
MPC		0.54
ClinPred		0.58	D
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.37
gMVP		0.22

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: chr17-47788624;