17-49720349-G-A

Position:

• chr17-49720349-G-A

Variant summary

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

The NM_030802.4(FAM117A):​c.550C>T​(p.His184Tyr) 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: 32)
• Consequence: FAM117A NM_030802.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.79

Genes affected

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

FAM117A (HGNC:):

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/exons	MANE	Protein	UniProt
FAM117A	NM_030802.4	c.550C>T	p.His184Tyr	missense_variant	4/8	ENST00000240364.7	NP_110429.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM117A	ENST00000240364.7	c.550C>T	p.His184Tyr	missense_variant	4/8	1	NM_030802.4	ENSP00000240364.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Dec 21, 2023

The c.550C>T (p.H184Y) alteration is located in exon 4 (coding exon 4) of the FAM117A gene. This alteration results from a C to T substitution at nucleotide position 550, causing the histidine (H) at amino acid position 184 to be replaced by a tyrosine (Y). 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	0.20
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.14
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T;T;T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.82	T;T;T
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.51	D;D;D
MetaSVM	Benign	-0.50	T
MutationAssessor	Pathogenic	2.9	M;.;.
PrimateAI	Uncertain	0.69	T
PROVEAN	Pathogenic	-4.8	D;D;D
REVEL	Benign	0.20
Sift	Benign	0.046	D;D;T
Sift4G	Uncertain	0.0030	D;.;.
Polyphen		0.86	P;.;.
Vest4		0.70
MutPred		0.37		Gain of phosphorylation at H184 (P = 0.0101);.;.;
MVP		0.19
MPC		1.3
ClinPred		0.98	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.28
gMVP		0.23

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: chr17-47797711;