16-4740311-G-C

Position:

• chr16-4740311-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_139170.3(DNAAF8):​c.435G>C​(p.Arg145Ser) 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: 31)
• Consequence: DNAAF8 NM_139170.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.875

Genes affected

DNAAF8 (HGNC:25081): (dynein axonemal assembly factor 8) Predicted to enable dynein complex binding activity. Predicted to be involved in outer dynein arm assembly. Located in dynein axonemal particle. [provided by Alliance of Genome Resources, Apr 2022]

DNAAF8 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.032241374).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAAF8	NM_139170.3	c.435G>C	p.Arg145Ser	missense_variant	4/10	ENST00000299320.10	NP_631909.2
DNAAF8	XM_017022975.2	c.504G>C	p.Arg168Ser	missense_variant	4/10		XP_016878464.1
DNAAF8	XM_005255144.4	c.21G>C	p.Arg7Ser	missense_variant	3/9		XP_005255201.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAAF8	ENST00000299320.10	c.435G>C	p.Arg145Ser	missense_variant	4/10	1	NM_139170.3	ENSP00000299320.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 31

Bravo AF: 0.0000113

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

Oct 22, 2021

The c.435G>C (p.R145S) alteration is located in exon 4 (coding exon 3) of the C16orf71 gene. This alteration results from a G to C substitution at nucleotide position 435, causing the arginine (R) at amino acid position 145 to be replaced by a serine (S). 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	0.18
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.062
DANN	Benign	0.82
DEOGEN2	Benign	0.0023	T;.;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.42	T;T;T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.032	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L;.;.
PROVEAN	Benign	-0.020	N;.;.
REVEL	Benign	0.012
Sift	Benign	0.89	T;.;.
Sift4G	Benign	0.40	T;T;T
Polyphen		0.015	B;.;.
Vest4		0.13
MutPred		0.14		Gain of phosphorylation at R145 (P = 0.0143);Gain of phosphorylation at R145 (P = 0.0143);.;
MVP		0.030
MPC		0.16
ClinPred		0.057	T
GERP RS		-3.8
Varity_R		0.10
gMVP		0.076

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

Other links and lift over

dbSNP: rs1279085136; hg19: chr16-4790312;