X-100914582-A-T

Position:

• chrX-100914582-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_212559.3(XKRX):​c.1106T>A​(p.Phe369Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: XKRX NM_212559.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.40

Genes affected

XKRX (HGNC:29845): (XK related X-linked) This gene encodes a protein that is related to a component of the XK/Kell complex of the Kell blood group system. The encoded protein includes several transmembrane domains, is known to be exposed to the cell surface, and may function as a membrane transporter. [provided by RefSeq, May 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12105787).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XKRX	NM_212559.3	c.1106T>A	p.Phe369Tyr	missense_variant	3/3	ENST00000372956.3	NP_997724.2
XKRX	XM_011530955.2	c.758T>A	p.Phe253Tyr	missense_variant	4/4		XP_011529257.1
XKRX	XM_017029517.2	c.494T>A	p.Phe165Tyr	missense_variant	2/2		XP_016885006.1
XKRX	XM_011530954.4	c.1106+39T>A		intron_variant			XP_011529256.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XKRX	ENST00000372956.3	c.1106T>A	p.Phe369Tyr	missense_variant	3/3	1	NM_212559.3	ENSP00000362047.2
XKRX	ENST00000468904.1	c.*417T>A		3_prime_UTR_variant	2/2	2		ENSP00000419884.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 19, 2022

The c.1106T>A (p.F369Y) alteration is located in exon 3 (coding exon 3) of the XKRX gene. This alteration results from a T to A substitution at nucleotide position 1106, causing the phenylalanine (F) at amino acid position 369 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	Benign	0.11
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	21
DANN	Benign	0.91
DEOGEN2	Benign	0.0074	T
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.1	L
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.47	N
REVEL	Benign	0.080
Sift	Benign	0.13	T
Sift4G	Benign	0.29	T
Polyphen		0.0010	B
Vest4		0.25
MutPred		0.49		Loss of ubiquitination at K368 (P = 0.0481);
MVP		0.41
MPC		0.11
ClinPred		0.23	T
GERP RS		3.3
Varity_R		0.14
gMVP		0.42

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-100169571;