2-127566730-C-T

Variant names:

• chr2-127566730-C-T
• rs370941935
• NM_001393586.1:c.373C>T

Variant summary

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

The NM_001393586.1(MYO7B):​c.373C>T​(p.Arg125Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,612,634 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000089 (0 hom.)
• Consequence: MYO7B NM_001393586.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.696
• Publications: 0 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: 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_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.373C>T	p.Arg125Cys	missense	Exon 5 of 48	NP_001380515.1	A0A8C8KL71
	MYO7B	NM_001080527.2		c.373C>T	p.Arg125Cys	missense	Exon 5 of 47	NP_001073996.1	Q6PIF6-1
	LOC105373609	NR_132317.1		n.83-1943G>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.373C>T	p.Arg125Cys	missense	Exon 5 of 48	ENSP00000386461.3	A0A8C8KL71
	MYO7B	ENST00000897059.1		c.373C>T	p.Arg125Cys	missense	Exon 5 of 48	ENSP00000567118.1
	MYO7B	ENST00000428314.5	TSL:5	c.373C>T	p.Arg125Cys	missense	Exon 5 of 47	ENSP00000415090.1	Q6PIF6-1

Frequencies

GnomAD3 genomes AF: 0.0000328 AC: 5 AN: 152258 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000808 AC: 2 AN: 247514 AF XY: 0.00

Gnomad AFR exome AF: 0.0000647

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000888

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000890 AC: 13 AN: 1460376 Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8 AN XY: 726516

African (AFR) AF: 0.0000597 AC: 2 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44682

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86218

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52292

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5766

European-Non Finnish (NFE) AF: 0.00000810 AC: 9 AN: 1111756

Other (OTH) AF: 0.00 AC: 0 AN: 60356

GnomAD4 genome AF: 0.0000328 AC: 5 AN: 152258 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74380

African (AFR) AF: 0.0000482 AC: 2 AN: 41464

American (AMR) AF: 0.00 AC: 0 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

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

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68044

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000342 Hom.: 0

Bravo AF: 0.0000227

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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	0.078
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T
Eigen	Benign	0.012
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.82	T
M_CAP	Uncertain	0.17	D
MetaRNN	Uncertain	0.49	T
MetaSVM	Uncertain	0.12	D
MutationAssessor	Uncertain	2.7	M
PhyloP100		0.70
PrimateAI	Benign	0.25	T
PROVEAN	Pathogenic	-5.6	D
REVEL	Uncertain	0.30
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.28
MutPred		0.59		Loss of disorder (P = 0.0443)
MVP		0.75
MPC		0.46
ClinPred		0.98	D
GERP RS		2.6
Varity_R		0.41
gMVP		0.67
Mutation Taster		=78/22	polymorphism

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: rs370941935; hg19: chr2-128324305; COSMIC: COSV101267792;