10-114836206-A-T

Position:

• chr10-114836206-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_020940.4(FHIP2A):​c.482A>T​(p.Lys161Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: FHIP2A NM_020940.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.29

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.825

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FHIP2A	NM_020940.4	c.482A>T	p.Lys161Met	missense_variant	5/17	ENST00000369248.9	NP_065991.3
FHIP2A	NM_001135051.2	c.482A>T	p.Lys161Met	missense_variant	5/17		NP_001128523.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FHIP2A	ENST00000369248.9	c.482A>T	p.Lys161Met	missense_variant	5/17	1	NM_020940.4	ENSP00000358251.4
FHIP2A	ENST00000369250.7	c.482A>T	p.Lys161Met	missense_variant	5/17	1		ENSP00000358253.3
FHIP2A	ENST00000710382.1	c.578A>T	p.Lys193Met	missense_variant	5/17			ENSP00000518239.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

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

Mar 31, 2024

The c.482A>T (p.K161M) alteration is located in exon 5 (coding exon 5) of the FAM160B1 gene. This alteration results from a A to T substitution at nucleotide position 482, causing the lysine (K) at amino acid position 161 to be replaced by a methionine (M). 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	Pathogenic	0.72
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T;.
Eigen	Pathogenic	0.80
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D;D
M_CAP	Benign	0.054	D
MetaRNN	Pathogenic	0.82	D;D
MetaSVM	Benign	-0.63	T
MutationAssessor	Uncertain	2.9	M;M
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-2.3	N;N
REVEL	Uncertain	0.35
Sift	Uncertain	0.0010	D;D
Sift4G	Uncertain	0.0080	D;D
Polyphen		1.0	D;D
Vest4		0.73
MutPred		0.73		Loss of ubiquitination at K161 (P = 0.0224);Loss of ubiquitination at K161 (P = 0.0224);
MVP		0.093
MPC		1.1
ClinPred		0.99	D
GERP RS		5.2
Varity_R		0.40
gMVP		0.76

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: chr10-116595965;