rs776160939

Variant names:

• chr2-127559727-C-A
• rs776160939
• NM_001393586.1:c.5C>A

Your query was ambiguous. Multiple possible variants found:

• chr2-127559727-C-A
• chr2-127559727-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001393586.1(MYO7B):​c.5C>A​(p.Ser2*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MYO7B NM_001393586.1 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.234
• Publications: 3 publications found

Genes affected

MYO7B (HGNC:7607): (myosin VIIB) The protein encoded by this gene is found in brush border microvilli of epithelial cells in the intestines and kidneys. The encoded protein is involved in linking protocadherins to the actin cytoskeleton and is essential for proper microvilli function. This protein aids in the accumulation of intermicrovillar adhesion components such as harmonin and ANKS4B, and this accumulation is necessary for normal brush border action. [provided by RefSeq, Jan 2017]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001393586.1. 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
	MYO7B	NM_001393586.1	MANE Select	c.5C>A	p.Ser2*	stop_gained	Exon 2 of 48	NP_001380515.1	A0A8C8KL71
	MYO7B	NM_001080527.2		c.5C>A	p.Ser2*	stop_gained	Exon 2 of 47	NP_001073996.1	Q6PIF6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO7B	ENST00000409816.8	TSL:1 MANE Select	c.5C>A	p.Ser2*	stop_gained	Exon 2 of 48	ENSP00000386461.3	A0A8C8KL71
	MYO7B	ENST00000897059.1		c.5C>A	p.Ser2*	stop_gained	Exon 2 of 48	ENSP00000567118.1
	MYO7B	ENST00000428314.5	TSL:5	c.5C>A	p.Ser2*	stop_gained	Exon 2 of 47	ENSP00000415090.1	Q6PIF6-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000251 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Pathogenic	35
DANN	Benign	0.97
Eigen	Benign	-0.061
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.18	N
PhyloP100		0.23
Vest4		0.072
GERP RS		2.0
Mutation Taster		=8/192	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.57		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.57		Position offset: 13

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

Other links and lift over

dbSNP: rs776160939; hg19: chr2-128317302;