Genetic Variant FTHL17:p.Gln8His (chrX-31071930-C-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_031894.3(FTHL17):c.24G>T(p.Gln8His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000011 in 1,094,216 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 21)

Exomes 𝑓: 0.000011 ( 0 hom. 4 hem. )

Consequence

FTHL17
NM_031894.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.263

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 -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.24641296).

BS2

High Hemizygotes in GnomAdExome4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FTHL17	NM_031894.3 link	c.24G>T	p.Gln8His	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.24G>T	p.Gln8His	missense_variant	Exon 1 of 1	6	NM_031894.3	ENSP00000368207.2		Q9BXU8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000167

AC:

AN:

180056

Hom.:

AF XY:

0.0000306

AC XY:

AN XY:

65456

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000366

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000250

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000110

AC:

AN:

1094216

Hom.:

Cov.:

AF XY:

0.0000111

AC XY:

AN XY:

360084

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000285

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000558

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000953

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.000130

Hom.:

Bravo

AF:

0.0000340

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 04, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.24G>T (p.Q8H) alteration is located in exon 1 (coding exon 1) of the FTHL17 gene. This alteration results from a G to T substitution at nucleotide position 24, causing the glutamine (Q) at amino acid position 8 to be replaced by a histidine (H). 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

0.23

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.52

CADD

Benign

5.6

DANN

Benign

0.95

DEOGEN2

Benign

0.14

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.38

M_CAP

Benign

0.041

MetaRNN

Benign

0.25

MetaSVM

Benign

-0.52

MutationAssessor

Pathogenic

3.1

PrimateAI

Benign

0.33

PROVEAN

Uncertain

-4.0

REVEL

Benign

0.19

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0020

Polyphen

0.99

Vest4

0.18

MutPred

0.37

Gain of glycosylation at S7 (P = 0.0985);

MVP

0.53

MPC

0.35

ClinPred

0.34

GERP RS

-6.4

Varity_R

0.30

gMVP

0.32

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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