Genetic Variant FTHL17:p.Asp14His (chrX-31071914-C-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_031894.3(FTHL17):c.40G>C(p.Asp14His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000182 in 1,206,959 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 7 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000090 ( 0 hom., 0 hem., cov: 22)

Exomes 𝑓: 0.000019 ( 0 hom. 7 hem. )

Consequence

FTHL17
NM_031894.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.82

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.023853868).

BP6

Variant X-31071914-C-G is Benign according to our data. Variant chrX-31071914-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2404559.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAdExome4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FTHL17	NM_031894.3 link	c.40G>C	p.Asp14His	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.40G>C	p.Asp14His	missense_variant	Exon 1 of 1	6	NM_031894.3	ENSP00000368207.2		Q9BXU8

Frequencies

GnomAD3 genomes

AF:

0.00000900

AC:

AN:

111064

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33264

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000950

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000990

AC:

AN:

181886

Hom.:

AF XY:

0.0000748

AC XY:

AN XY:

66866

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000658

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000192

AC:

AN:

1095895

Hom.:

Cov.:

AF XY:

0.0000194

AC XY:

AN XY:

361455

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000540

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:

0.00

GnomAD4 genome

AF:

0.00000900

AC:

AN:

111064

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33264

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000950

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000264

ExAC

AF:

0.0000412

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Aug 09, 2021

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.72

CADD

Benign

2.2

DANN

Benign

0.087

DEOGEN2

Benign

0.0049

FATHMM_MKL

Benign

0.030

LIST_S2

Benign

0.65

M_CAP

Benign

0.0062

MetaRNN

Benign

0.024

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-2.3

PrimateAI

Benign

0.35

PROVEAN

Benign

6.1

REVEL

Benign

0.092

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0010

Vest4

0.062

MutPred

0.44

Gain of helix (P = 0.132);

MVP

0.61

MPC

0.37

ClinPred

0.014

GERP RS

0.57

Varity_R

0.055

gMVP

0.41

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