17-32654595-C-T

Position:

• chr17-32654595-C-T

Variant summary

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

The NM_015194.3(MYO1D):​c.2372G>A​(p.Ser791Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,150 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MYO1D NM_015194.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.818

Genes affected

MYO1D (HGNC:7598): (myosin ID) Enables protein domain specific binding activity. Predicted to be involved in actin filament organization; early endosome to recycling endosome transport; and vesicle transport along actin filament. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

(HGNC:):

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=0.073678136).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO1D	NM_015194.3	c.2372G>A	p.Ser791Asn	missense_variant	18/22	ENST00000318217.10	NP_056009.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO1D	ENST00000318217.10	c.2372G>A	p.Ser791Asn	missense_variant	18/22	1	NM_015194.3	ENSP00000324527	P1
	ENST00000582272.1	n.141+22116C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460150 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726322

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

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

Jan 04, 2024

The c.2372G>A (p.S791N) alteration is located in exon 18 (coding exon 18) of the MYO1D gene. This alteration results from a G to A substitution at nucleotide position 2372, causing the serine (S) at amino acid position 791 to be replaced by an asparagine (N). 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	0.072
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	14
DANN	Benign	0.81
DEOGEN2	Benign	0.042	T;T;T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.40
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.84	T;T;T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.074	T;T;T
MetaSVM	Benign	-0.75	T
MutationAssessor	Benign	0.65	N;.;.
MutationTaster	Benign	0.56	N;N;N
PrimateAI	Benign	0.38	T
PROVEAN	Benign	0.47	N;.;.
REVEL	Benign	0.14
Sift	Benign	0.66	T;.;.
Sift4G	Benign	0.65	T;T;T
Polyphen		0.0	B;.;.
Vest4		0.13
MutPred		0.23		Gain of MoRF binding (P = 0.1048);.;Gain of MoRF binding (P = 0.1048);
MVP		0.75
MPC		0.26
ClinPred		0.11	T
GERP RS		1.1
Varity_R		0.021
gMVP		0.24

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr17-30981613;