10-114842951-G-A

Position:

• chr10-114842951-G-A

Variant summary

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

The NM_020940.4(FHIP2A):​c.541G>A​(p.Ala181Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FHIP2A NM_020940.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.96

Genes affected

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

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=0.10381672).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FHIP2A	NM_020940.4	c.541G>A	p.Ala181Thr	missense_variant	6/17	ENST00000369248.9	NP_065991.3
FHIP2A	NM_001135051.2	c.541G>A	p.Ala181Thr	missense_variant	6/17		NP_001128523.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FHIP2A	ENST00000369248.9	c.541G>A	p.Ala181Thr	missense_variant	6/17	1	NM_020940.4	ENSP00000358251.4
FHIP2A	ENST00000369250.7	c.541G>A	p.Ala181Thr	missense_variant	6/17	1		ENSP00000358253.3
FHIP2A	ENST00000710382.1	c.637G>A	p.Ala213Thr	missense_variant	6/17			ENSP00000518239.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

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

Sep 03, 2024

The c.541G>A (p.A181T) alteration is located in exon 6 (coding exon 6) of the FAM160B1 gene. This alteration results from a G to A substitution at nucleotide position 541, causing the alanine (A) at amino acid position 181 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	0.068
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.015	T;.
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.19
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.50	T;T
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.10	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L;L
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.19	N;N
REVEL	Benign	0.046
Sift	Benign	0.41	T;T
Sift4G	Benign	0.36	T;T
Polyphen		0.015	B;B
Vest4		0.037
MutPred		0.49		Loss of loop (P = 0.0603);Loss of loop (P = 0.0603);
MVP		0.12
MPC		0.25
ClinPred		0.32	T
GERP RS		2.9
Varity_R		0.032
gMVP		0.33

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: chr10-116602710;