Genetic Variant NM_031894.3:c.164A>G (chrX-31071790-T-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_031894.3(FTHL17):c.164A>G(p.Tyr55Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000909 in 1,209,695 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000054 ( 0 hom., 2 hem., cov: 23)

Exomes 𝑓: 0.0000046 ( 0 hom. 2 hem. )

Consequence

FTHL17
NM_031894.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.851

Variant links:

Genes affected

FTHL17 (HGNC:3987): (ferritin heavy chain like 17) This gene encodes a ferritin heavy chain-like protein. This gene is primarily expressed in embryonic germ cells. The encoded protein may lack ferroxidase activity. Multiple pseudogenes of this gene are found on chromosome X. [provided by RefSeq, Oct 2016]

FTHL17 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High Hemizygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FTHL17	NM_031894.3 link	c.164A>G	p.Tyr55Cys	missense_variant	Exon 1 of 1	ENST00000359202.5	NP_114100.1	Q9BXU8A0A384NPV7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FTHL17	ENST00000359202.5 link	c.164A>G	p.Tyr55Cys	missense_variant	Exon 1 of 1	6	NM_031894.3	ENSP00000368207.2		Q9BXU8

Frequencies

GnomAD3 genomes

AF:

0.0000538

AC:

AN:

111612

Hom.:

Cov.:

AF XY:

0.0000592

AC XY:

AN XY:

33796

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000285

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000376

Gnomad OTH

AF:

0.000672

GnomAD3 exomes

AF:

0.0000109

AC:

AN:

183485

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

67923

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000365

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000524

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000455

AC:

AN:

1098083

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

363439

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000568

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000238

Gnomad4 OTH exome

AF:

0.0000217

GnomAD4 genome

AF:

0.0000538

AC:

AN:

111612

Hom.:

Cov.:

AF XY:

0.0000592

AC XY:

AN XY:

33796

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000285

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000376

Gnomad4 OTH

AF:

0.000672

Bravo

AF:

0.00000756

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 23, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.164A>G (p.Y55C) alteration is located in exon 1 (coding exon 1) of the FTHL17 gene. This alteration results from a A to G substitution at nucleotide position 164, causing the tyrosine (Y) at amino acid position 55 to be replaced by a cysteine (C). 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

0.25

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.38

CADD

Benign

9.9

DANN

Benign

0.85

DEOGEN2

Benign

0.18

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.69

M_CAP

Benign

0.036

MetaRNN

Uncertain

0.46

MetaSVM

Benign

-0.67

MutationAssessor

Uncertain

2.3

PrimateAI

Benign

0.33

PROVEAN

Pathogenic

-6.6

REVEL

Benign

0.24

Sift

Benign

0.041

Sift4G

Uncertain

0.035

Polyphen

0.29

Vest4

0.080

MutPred

0.78

Loss of stability (P = 0.2002);

MVP

0.66

MPC

0.55

ClinPred

0.20

GERP RS

0.75

Varity_R

0.40

gMVP

0.75

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over