4-151566279-C-T

Variant names:

• chr4-151566279-C-T
• rs188418316
• NM_001109977.3:c.20C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001109977.3(FHIP1A):​c.20C>T​(p.Thr7Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000306 in 1,549,950 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00029 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00031 (0 hom.)
• Consequence: FHIP1A NM_001109977.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.05
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.057543248).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001109977.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FHIP1A	NM_001109977.3	MANE Select	c.20C>T	p.Thr7Ile	missense	Exon 4 of 14	NP_001103447.1	Q05DH4
	FHIP1A	NM_001348694.2		c.20C>T	p.Thr7Ile	missense	Exon 3 of 13	NP_001335623.1	Q05DH4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FHIP1A	ENST00000435205.6	TSL:5 MANE Select	c.20C>T	p.Thr7Ile	missense	Exon 4 of 14	ENSP00000413196.1	Q05DH4
	FHIP1A	ENST00000505231.1	TSL:5	c.20C>T	p.Thr7Ile	missense	Exon 2 of 12	ENSP00000421580.1	Q05DH4
	FHIP1A	ENST00000883036.1		c.20C>T	p.Thr7Ile	missense	Exon 2 of 12	ENSP00000553095.1

Frequencies

GnomAD3 genomes AF: 0.000289 AC: 44 AN: 152106 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000943

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000338

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000205 AC: 32 AN: 156270 AF XY: 0.000157

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000122

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000713

Gnomad NFE exome AF: 0.000248

Gnomad OTH exome AF: 0.000458

GnomAD4 exome AF: 0.000308 AC: 430 AN: 1397726 Hom.: 0 Cov.: 29 AF XY: 0.000300 AC XY: 207 AN XY: 689398

African (AFR) AF: 0.0000634 AC: 2 AN: 31538

American (AMR) AF: 0.000112 AC: 4 AN: 35600

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25136

East Asian (EAS) AF: 0.00 AC: 0 AN: 35704

South Asian (SAS) AF: 0.00 AC: 0 AN: 79114

European-Finnish (FIN) AF: 0.000568 AC: 28 AN: 49282

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5688

European-Non Finnish (NFE) AF: 0.000351 AC: 378 AN: 1077732

Other (OTH) AF: 0.000311 AC: 18 AN: 57932

GnomAD4 genome AF: 0.000289 AC: 44 AN: 152224 Hom.: 0 Cov.: 32 AF XY: 0.000309 AC XY: 23 AN XY: 74420

African (AFR) AF: 0.000120 AC: 5 AN: 41530

American (AMR) AF: 0.000393 AC: 6 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.000943 AC: 10 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000338 AC: 23 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000197 Hom.: 0

Bravo AF: 0.000249

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000314 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	19
DANN	Benign	0.58
DEOGEN2	Benign	0.0067	T
Eigen	Benign	0.029
Eigen_PC	Benign	0.11
FATHMM_MKL	Benign	0.57	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.058	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L
PhyloP100		3.0
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.055
Sift	Benign	0.12	T
Sift4G	Benign	0.064	T
Polyphen		0.72	P
Vest4		0.20
MVP		0.12
ClinPred		0.090	T
GERP RS		5.0
Varity_R		0.082
gMVP		0.28
Mutation Taster		=90/10	polymorphism

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

Other links and lift over

dbSNP: rs188418316; hg19: chr4-152487431; COSMIC: COSV99064861; COSMIC: COSV99064861;