10-114846188-A-G

Position:

• chr10-114846188-A-G

Variant summary

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

The NM_020940.4(FHIP2A):​c.1219A>G​(p.Ile407Val) variant causes a missense change involving the alteration of a conserved nucleotide. 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: FHIP2A NM_020940.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.96

Genes affected

FHIP2A (HGNC:29320): (FHF complex subunit HOOK interacting protein 2A)

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
FHIP2A	NM_020940.4	c.1219A>G	p.Ile407Val	missense_variant	10/17	ENST00000369248.9	NP_065991.3
FHIP2A	NM_001135051.2	c.1219A>G	p.Ile407Val	missense_variant	10/17		NP_001128523.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FHIP2A	ENST00000369248.9	c.1219A>G	p.Ile407Val	missense_variant	10/17	1	NM_020940.4	ENSP00000358251.4
FHIP2A	ENST00000369250.7	c.1219A>G	p.Ile407Val	missense_variant	10/17	1		ENSP00000358253.3
FHIP2A	ENST00000710382.1	c.1315A>G	p.Ile439Val	missense_variant	10/17			ENSP00000518239.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

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 12, 2023

The c.1219A>G (p.I407V) alteration is located in exon 10 (coding exon 10) of the FAM160B1 gene. This alteration results from a A to G substitution at nucleotide position 1219, causing the isoleucine (I) at amino acid position 407 to be replaced by a valine (V). 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	0.27
BayesDel_addAF	Benign	-0.066	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.017	T;.
Eigen	Benign	0.054
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.86	D;D
M_CAP	Benign	0.0061	T
MetaRNN	Uncertain	0.45	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L;L
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	0.060	N;N
REVEL	Benign	0.26
Sift	Benign	0.32	T;T
Sift4G	Benign	0.53	T;T
Polyphen		0.097	B;B
Vest4		0.63
MutPred		0.75		Gain of catalytic residue at I407 (P = 0.0099);Gain of catalytic residue at I407 (P = 0.0099);
MVP		0.10
MPC		0.37
ClinPred		0.66	D
GERP RS		6.2
Varity_R		0.098
gMVP		0.16

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: chr10-116605947;