17-7858475-G-A

Variant names:

• chr17-7858475-G-A
• NM_144607.6:c.233G>A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_144607.6(CYB5D1):​c.233G>A​(p.Arg78Lys) 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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CYB5D1 NM_144607.6 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.343

Genes affected

CYB5D1 (HGNC:26516): (cytochrome b5 domain containing 1) Predicted to enable metal ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

NAA38 (HGNC:28212): (N-alpha-acetyltransferase 38, NatC auxiliary subunit) Involved in negative regulation of apoptotic process. Located in cytoplasm and nucleoplasm. Part of NatC complex. Colocalizes with polysome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.011277586).
• BP6: Variant 17-7858475-G-A is Benign according to our data. Variant chr17-7858475-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2273414.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYB5D1	NM_144607.6	c.233G>A	p.Arg78Lys	missense_variant	Exon 2 of 4	ENST00000332439.5	NP_653208.2
CYB5D1	NM_001330110.2	c.233G>A	p.Arg78Lys	missense_variant	Exon 2 of 4		NP_001317039.1
NAA38	NM_001330111.2	c.4-1277C>T		intron_variant	Intron 3 of 4		NP_001317040.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYB5D1	ENST00000332439.5	c.233G>A	p.Arg78Lys	missense_variant	Exon 2 of 4	1	NM_144607.6	ENSP00000331479.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Jan 26, 2022

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	0.063
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.47
DANN	Benign	0.84
DEOGEN2	Benign	0.00038	.;T
Eigen	Benign	-2.0
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.0072	N
LIST_S2	Benign	0.26	T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.011	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.99	N;N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.35	.;N
REVEL	Benign	0.17
Sift	Benign	1.0	.;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;B
Vest4		0.058
MutPred		0.32		Gain of ubiquitination at R78 (P = 0.0539);Gain of ubiquitination at R78 (P = 0.0539);
MVP		0.13
MPC		0.65
ClinPred		0.090	T
GERP RS		-9.5
Varity_R		0.060
gMVP		0.50

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: chr17-7761793;