NM_007124.3:c.530C>G

Variant names:

• chr6-144426411-C-G
• rs550714040
• NM_007124.3:c.530C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_007124.3(UTRN):​c.530C>G​(p.Thr177Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T177N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: UTRN NM_007124.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.05
• Publications: 0 publications found

Genes affected

UTRN (HGNC:12635): (utrophin) This gene shares both structural and functional similarities with the dystrophin gene. It contains an actin-binding N-terminus, a triple coiled-coil repeat central region, and a C-terminus that consists of protein-protein interaction motifs which interact with dystroglycan protein components. The protein encoded by this gene is located at the neuromuscular synapse and myotendinous junctions, where it participates in post-synaptic membrane maintenance and acetylcholine receptor clustering. Mouse studies suggest that this gene may serve as a functional substitute for the dystrophin gene and therefore, may serve as a potential therapeutic alternative to muscular dystrophy which is caused by mutations in the dystrophin gene. Alternative splicing of the utrophin gene has been described; however, the full-length nature of these variants has not yet been determined. [provided by RefSeq, Jul 2008]

UTRN Gene-Disease associations (from GenCC):

• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007124.3. 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
	UTRN	NM_007124.3	MANE Select	c.530C>G	p.Thr177Ser	missense	Exon 7 of 75	NP_009055.2	P46939-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UTRN	ENST00000367545.8	TSL:5 MANE Select	c.530C>G	p.Thr177Ser	missense	Exon 7 of 75	ENSP00000356515.3	P46939-1
	UTRN	ENST00000421035.2	TSL:2	c.*83C>G		downstream_gene	N/A	ENSP00000396276.2	A0A0A0MSM3
	UTRN	ENST00000628146.2	TSL:2	c.*53C>G		downstream_gene	N/A	ENSP00000487153.1	A0A0D9SG57

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.70	D
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.045	D
MetaRNN	Uncertain	0.65	D
MetaSVM	Uncertain	0.43	D
MutationAssessor	Benign	0.24	N
PhyloP100		6.0
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-1.7	N
REVEL	Uncertain	0.59
Sift	Benign	0.21	T
Polyphen		0.99	D
Vest4		0.61
MutPred		0.51		Loss of helix (P = 0.2022)
MVP		0.84
MPC		0.55
ClinPred		0.88	D
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.28
gMVP		0.38
Mutation Taster		=43/57	disease causing

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

Other links and lift over

dbSNP: rs550714040; hg19: chr6-144747547;