Genetic Variant NM_032608.7:c.4239G>A (chr22-25877973-G-A) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_032608.7(MYO18B):c.4239G>A(p.Thr1413Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000773 in 1,423,798 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000077 ( 0 hom. )

Consequence

MYO18B
NM_032608.7 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.222

Variant links:

Genes affected

MYO18B (HGNC:18150): (myosin XVIIIB) The protein encoded by this gene may regulate muscle-specific genes when in the nucleus and may influence intracellular trafficking when in the cytoplasm. The encoded protein functions as a homodimer and may interact with F actin. Mutations in this gene are associated with lung cancer. [provided by RefSeq, Jul 2008]

MYO18B links:

MYO18B-AS1 (HGNC:40831): (MYO18B antisense RNA 1)

MYO18B-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 22-25877973-G-A is Benign according to our data. Variant chr22-25877973-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1590472.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.222 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO18B	NM_032608.7 link	c.4239G>A	p.Thr1413Thr	synonymous_variant	Exon 25 of 44	ENST00000335473.12	NP_115997.5	Q8IUG5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MYO18B	ENST00000335473.12 link	c.4239G>A	p.Thr1413Thr	synonymous_variant	Exon 25 of 44	1	NM_032608.7	ENSP00000334563.8	Q8IUG5-1
MYO18B	ENST00000407587.6 link	c.4242G>A	p.Thr1414Thr	synonymous_variant	Exon 25 of 44	1		ENSP00000386096.2	Q8IUG5-3
MYO18B	ENST00000536101.5 link	c.4239G>A	p.Thr1413Thr	synonymous_variant	Exon 25 of 43	1		ENSP00000441229.1	Q8IUG5-1
MYO18B	ENST00000539302.5 link	n.*1697G>A		non_coding_transcript_exon_variant	Exon 23 of 42	1		ENSP00000437587.1	F5H6I8
MYO18B	ENST00000539302.5 link	n.*1697G>A		3_prime_UTR_variant	Exon 23 of 42	1		ENSP00000437587.1	F5H6I8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000103

AC:

AN:

193396

Hom.:

AF XY:

0.00000973

AC XY:

AN XY:

102780

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000241

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000773

AC:

AN:

1423798

Hom.:

Cov.:

AF XY:

0.00000852

AC XY:

AN XY:

704278

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.0000101

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000282

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Nov 23, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

2.3

DANN

Benign

0.39

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