NM_001145018.3:c.341G>T

Variant names:

• chr11-119193159-C-A
• NM_001145018.3:c.341G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001145018.3(DRC12):​c.341G>T​(p.Gly114Val) 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DRC12 NM_001145018.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.02
• Publications: 0 publications found

Genes affected

DRC12 (HGNC:27446): (dynein regulatory complex subunit 12 homolog) Enables identical protein binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.054204315).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145018.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DRC12	NM_001145018.3	MANE Select	c.341G>T	p.Gly114Val	missense	Exon 5 of 7	NP_001138490.1	Q494R4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DRC12	ENST00000503566.7	TSL:5 MANE Select	c.341G>T	p.Gly114Val	missense	Exon 5 of 7	ENSP00000423567.2	Q494R4-1
	DRC12	ENST00000927900.1		c.362G>T	p.Gly121Val	missense	Exon 4 of 6	ENSP00000597959.1
	DRC12	ENST00000415318.2	TSL:5	c.341G>T	p.Gly114Val	missense	Exon 6 of 8	ENSP00000445431.1	Q494R4-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	9.9
DANN	Benign	0.62
DEOGEN2	Benign	0.0030	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.037	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.054	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		1.0
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.038
Sift	Benign	0.055	T
Sift4G	Benign	0.23	T
Polyphen		0.0	B
Vest4		0.11
MutPred		0.16		Gain of loop (P = 0.0435)
MVP		0.12
MPC		0.17
ClinPred		0.034	T
GERP RS		1.1
Varity_R		0.055
gMVP		0.089
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr11-119063869;