NM_001393586.1:c.290A>T

Variant names:

• chr2-127566647-A-T
• rs201898602
• NM_001393586.1:c.290A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001393586.1(MYO7B):​c.290A>T​(p.Tyr97Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000198 in 1,583,616 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00057 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00016 (0 hom.)
• Consequence: MYO7B NM_001393586.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.31
• Publications: 2 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]

LOC105373609 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.26135284).

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.290A>T	p.Tyr97Phe	missense	Exon 5 of 48	NP_001380515.1	A0A8C8KL71
	MYO7B	NM_001080527.2		c.290A>T	p.Tyr97Phe	missense	Exon 5 of 47	NP_001073996.1	Q6PIF6-1
	LOC105373609	NR_132317.1		n.83-1860T>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO7B	ENST00000409816.8	TSL:1 MANE Select	c.290A>T	p.Tyr97Phe	missense	Exon 5 of 48	ENSP00000386461.3	A0A8C8KL71
	MYO7B	ENST00000897059.1		c.290A>T	p.Tyr97Phe	missense	Exon 5 of 48	ENSP00000567118.1
	MYO7B	ENST00000428314.5	TSL:5	c.290A>T	p.Tyr97Phe	missense	Exon 5 of 47	ENSP00000415090.1	Q6PIF6-1

Frequencies

GnomAD3 genomes AF: 0.000565 AC: 86 AN: 152168 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00174

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000229 AC: 47 AN: 204822 AF XY: 0.000145

Gnomad AFR exome AF: 0.00157

Gnomad AMR exome AF: 0.000441

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000143

Gnomad OTH exome AF: 0.000382

GnomAD4 exome AF: 0.000159 AC: 227 AN: 1431448 Hom.: 0 Cov.: 31 AF XY: 0.000132 AC XY: 94 AN XY: 709802

African (AFR) AF: 0.00195 AC: 64 AN: 32902

American (AMR) AF: 0.000348 AC: 14 AN: 40258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25376

East Asian (EAS) AF: 0.00 AC: 0 AN: 38260

South Asian (SAS) AF: 0.00 AC: 0 AN: 82270

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49122

Middle Eastern (MID) AF: 0.00107 AC: 6 AN: 5604

European-Non Finnish (NFE) AF: 0.000110 AC: 121 AN: 1098272

Other (OTH) AF: 0.000370 AC: 22 AN: 59384

GnomAD4 genome AF: 0.000565 AC: 86 AN: 152168 Hom.: 0 Cov.: 33 AF XY: 0.000484 AC XY: 36 AN XY: 74324

African (AFR) AF: 0.00174 AC: 72 AN: 41440

American (AMR) AF: 0.000327 AC: 5 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68020

Other (OTH) AF: 0.000478 AC: 1 AN: 2090

Alfa AF: 0.000180 Hom.: 0

Bravo AF: 0.000623

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.000500 AC: 2

ESP6500EA AF: 0.000241 AC: 2

ExAC AF: 0.000157 AC: 19

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	0.11
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.38	T
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.049	D
MetaRNN	Benign	0.26	T
MetaSVM	Uncertain	0.21	D
MutationAssessor	Uncertain	2.2	M
PhyloP100		7.3
PrimateAI	Uncertain	0.78	T
PROVEAN	Uncertain	-3.5	D
REVEL	Pathogenic	0.69
Sift	Benign	0.062	T
Sift4G	Benign	0.080	T
Polyphen		1.0	D
Vest4		0.65
MVP		0.76
MPC		0.43
ClinPred		0.051	T
GERP RS		5.5
Varity_R		0.42
gMVP		0.58
Mutation Taster		=40/60	disease causing

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

dbSNP: rs201898602; hg19: chr2-128324222;