chrX-107213005-G-C

Position:

• chrX-107213005-G-C

Variant summary

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

The NM_173494.2(DNAAF6):​c.130G>C​(p.Glu44Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: DNAAF6 NM_173494.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.93

Genes affected

DNAAF6 (HGNC:28570): (dynein axonemal assembly factor 6) Enables dynein intermediate chain binding activity. Involved in flagellated sperm motility; inner dynein arm assembly; and outer dynein arm assembly. Located in trans-Golgi network. Implicated in primary ciliary dyskinesia 36. [provided by Alliance of Genome Resources, Apr 2022]

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=0.25811696).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAAF6	NM_173494.2	c.130G>C	p.Glu44Gln	missense_variant	2/7	ENST00000372453.8	NP_775765.1
DNAAF6	NM_001169154.2	c.130G>C	p.Glu44Gln	missense_variant	3/8		NP_001162625.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAAF6	ENST00000372453.8	c.130G>C	p.Glu44Gln	missense_variant	2/7	1	NM_173494.2	ENSP00000361531.3
DNAAF6	ENST00000336387.4	c.130G>C	p.Glu44Gln	missense_variant	2/7	5		ENSP00000337757.4
DNAAF6	ENST00000535523.6	c.130G>C	p.Glu44Gln	missense_variant	3/8	5		ENSP00000441930.1
DNAAF6	ENST00000688816.1	c.130G>C	p.Glu44Gln	missense_variant	2/6			ENSP00000508655.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 07, 2024

This sequence change replaces glutamic acid, which is acidic and polar, with glutamine, which is neutral and polar, at codon 44 of the PIH1D3 protein (p.Glu44Gln). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PIH1D3-related conditions. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Uncertain	0.034	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.028	T;T;T
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.58	T;.;.
M_CAP	Uncertain	0.23	D
MetaRNN	Benign	0.26	T;T;T
MetaSVM	Uncertain	-0.19	T
MutationAssessor	Pathogenic	3.0	M;M;M
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.4	N;N;N
REVEL	Benign	0.13
Sift	Benign	0.079	T;T;T
Sift4G	Uncertain	0.035	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.22
MutPred		0.23		Loss of solvent accessibility (P = 0.0174);Loss of solvent accessibility (P = 0.0174);Loss of solvent accessibility (P = 0.0174);
MVP		0.50
MPC		0.37
ClinPred		0.96	D
GERP RS		5.4
Varity_R		0.35
gMVP		0.093

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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-106456235;