chr4-151566353-C-T

Variant names:

• chr4-151566353-C-T
• rs1415904460
• NM_001109977.3:c.94C>T

Variant summary

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

The NM_001109977.3(FHIP1A):​c.94C>T​(p.His32Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000000718 in 1,392,998 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: FHIP1A NM_001109977.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.11

Genes affected

FHIP1A (HGNC:34237): (FHF complex subunit HOOK interacting protein 1A) Involved in protein localization to perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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 rank	MANE	Protein	UniProt
FHIP1A	NM_001109977.3	c.94C>T	p.His32Tyr	missense_variant	Exon 4 of 14	ENST00000435205.6	NP_001103447.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FHIP1A	ENST00000435205.6	c.94C>T	p.His32Tyr	missense_variant	Exon 4 of 14	5	NM_001109977.3	ENSP00000413196.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.18e-7 AC: 1 AN: 1392998 Hom.: 0 Cov.: 27 AF XY: 0.00000145 AC XY: 1 AN XY: 687500

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000126

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000301 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 08, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.94C>T (p.H32Y) alteration is located in exon 4 (coding exon 1) of the FAM160A1 gene. This alteration results from a C to T substitution at nucleotide position 94, causing the histidine (H) at amino acid position 32 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	Pathogenic	0.95
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.10
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	.;T;T;.;T
Eigen	Pathogenic	0.79
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.94	D;D;D;D;.
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.67	D;D;D;D;D
MetaSVM	Benign	-0.84	T
MutationAssessor	Uncertain	2.5	.;M;.;.;M
PrimateAI	Uncertain	0.73	T
PROVEAN	Pathogenic	-6.0	D;D;D;D;D
REVEL	Uncertain	0.36
Sift	Pathogenic	0.0	D;D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D;D
Polyphen		1.0	.;D;.;.;D
Vest4		0.72, 0.71
MutPred		0.68		Loss of ubiquitination at K30 (P = 0.1202);Loss of ubiquitination at K30 (P = 0.1202);Loss of ubiquitination at K30 (P = 0.1202);Loss of ubiquitination at K30 (P = 0.1202);Loss of ubiquitination at K30 (P = 0.1202);
MVP		0.17
ClinPred		0.99	D
GERP RS		5.9
Varity_R		0.82
gMVP		0.84

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

LitVar

Other links and lift over

dbSNP: rs1415904460; hg19: chr4-152487505;