17-49711262-A-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 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
• Publications: 0 publications found

Genes affected

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

ENSG00000250751 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15760282).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030802.4. 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
	FAM117A	NM_030802.4	MANE Select	c.1355T>C	p.Met452Thr	missense	Exon 8 of 8	NP_110429.1	Q9C073-1
	FAM117A	NM_001411126.1		c.539T>C	p.Met180Thr	missense	Exon 8 of 8	NP_001398055.1	Q9C073-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM117A	ENST00000240364.7	TSL:1 MANE Select	c.1355T>C	p.Met452Thr	missense	Exon 8 of 8	ENSP00000240364.2	Q9C073-1
	FAM117A	ENST00000513602.5	TSL:2	c.539T>C	p.Met180Thr	missense	Exon 8 of 8	ENSP00000465808.1	Q9C073-2
	ENSG00000250751	ENST00000512720.1	TSL:3	n.142+2787A>G		intron	N/A

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

African (AFR) AF: 0.00 AC: 0 AN: 33162

American (AMR) AF: 0.00 AC: 0 AN: 43894

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25534

East Asian (EAS) AF: 0.00 AC: 0 AN: 39532

South Asian (SAS) AF: 0.00 AC: 0 AN: 85178

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52912

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4792

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1105232

Other (OTH) AF: 0.00 AC: 0 AN: 59712

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		5.4
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.060
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.050	T
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

Other links and lift over

hg19: chr17-47788624;