chr7-95813325-G-C

Position:

• chr7-95813325-G-C

Variant summary

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

The NM_001135556.2(DYNC1I1):​c.302G>C​(p.Gly101Ala) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 29)
• Consequence: DYNC1I1 NM_001135556.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.36

Genes affected

DYNC1I1 (HGNC:2963): (dynein cytoplasmic 1 intermediate chain 1) Enables spectrin binding activity. Involved in vesicle transport along microtubule. Located in several cellular components, including kinetochore; recycling endosome; and spindle pole. [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=0.1921981).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DYNC1I1	NM_001135556.2	c.302G>C	p.Gly101Ala	missense_variant	4/17	ENST00000447467.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DYNC1I1	ENST00000447467.6	c.302G>C	p.Gly101Ala	missense_variant	4/17	1	NM_001135556.2	P3

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 29

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

Nov 23, 2022

The c.353G>C (p.G118A) alteration is located in exon 4 (coding exon 3) of the DYNC1I1 gene. This alteration results from a G to C substitution at nucleotide position 353, causing the glycine (G) at amino acid position 118 to be replaced by an alanine (A). 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	0.073
BayesDel_addAF	Benign	-0.077	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	23
DANN	Benign	0.95
DEOGEN2	Benign	0.0071	T;.;T;.;.;.;.;T;.
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.072
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.71	T;.;T;T;T;T;D;D;T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.19	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	-0.40	.;.;N;.;N;.;.;.;.
MutationTaster	Benign	0.99	D;D;D;D;D;D;D
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-0.65	.;N;N;.;N;N;N;N;N
REVEL	Benign	0.12
Sift	Benign	0.69	.;T;T;.;T;T;D;T;T
Sift4G	Benign	0.26	T;T;T;T;T;T;T;T;T
Polyphen		0.0	.;B;B;.;.;B;.;.;B
Vest4		0.16
MutPred		0.32		.;.;Loss of catalytic residue at G118 (P = 0.1562);.;Loss of catalytic residue at G118 (P = 0.1562);.;.;.;.;
MVP		0.67
MPC		0.60
ClinPred		0.80	D
GERP RS		4.6
Varity_R		0.18
gMVP		0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: chr7-95442637;