chr2-127569812-C-T

Variant names:

• chr2-127569812-C-T
• rs190814907
• NM_001393586.1:c.494C>T

Variant summary

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

The NM_001393586.1(MYO7B):​c.494C>T​(p.Thr165Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000362 in 1,612,756 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00029 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00037 (0 hom.)
• Consequence: MYO7B NM_001393586.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.79
• 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: Uncertain_significance. The variant received 0 ACMG points.

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.494C>T	p.Thr165Met	missense	Exon 6 of 48	NP_001380515.1	A0A8C8KL71
	MYO7B	NM_001080527.2		c.494C>T	p.Thr165Met	missense	Exon 6 of 47	NP_001073996.1	Q6PIF6-1
	LOC105373609	NR_132317.1		n.82+1069G>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.494C>T	p.Thr165Met	missense	Exon 6 of 48	ENSP00000386461.3	A0A8C8KL71
	MYO7B	ENST00000897059.1		c.494C>T	p.Thr165Met	missense	Exon 6 of 48	ENSP00000567118.1
	MYO7B	ENST00000428314.5	TSL:5	c.494C>T	p.Thr165Met	missense	Exon 6 of 47	ENSP00000415090.1	Q6PIF6-1

Frequencies

GnomAD3 genomes AF: 0.000289 AC: 44 AN: 152112 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00105

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: 0.000367

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000419 AC: 104 AN: 248200 AF XY: 0.000371

Gnomad AFR exome AF: 0.000130

Gnomad AMR exome AF: 0.00126

Gnomad ASJ exome AF: 0.000199

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000435

Gnomad OTH exome AF: 0.00100

GnomAD4 exome AF: 0.000370 AC: 540 AN: 1460526 Hom.: 0 Cov.: 30 AF XY: 0.000314 AC XY: 228 AN XY: 726516

African (AFR) AF: 0.0000299 AC: 1 AN: 33452

American (AMR) AF: 0.00128 AC: 57 AN: 44654

Ashkenazi Jewish (ASJ) AF: 0.0000766 AC: 2 AN: 26104

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39650

South Asian (SAS) AF: 0.0000349 AC: 3 AN: 86078

European-Finnish (FIN) AF: 0.0000375 AC: 2 AN: 53370

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5762

European-Non Finnish (NFE) AF: 0.000410 AC: 456 AN: 1111138

Other (OTH) AF: 0.000265 AC: 16 AN: 60318

GnomAD4 genome AF: 0.000289 AC: 44 AN: 152230 Hom.: 0 Cov.: 32 AF XY: 0.000322 AC XY: 24 AN XY: 74428

African (AFR) AF: 0.0000722 AC: 3 AN: 41532

American (AMR) AF: 0.00105 AC: 16 AN: 15290

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000368 AC: 25 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2106

Alfa AF: 0.000402 Hom.: 0

Bravo AF: 0.000487

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000477 AC: 4

ExAC AF: 0.000446 AC: 54

EpiCase AF: 0.000492

EpiControl AF: 0.000356

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	Uncertain	0.56
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Pathogenic	0.40
CADD	Pathogenic	32
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.61	D
Eigen	Pathogenic	1.1
Eigen_PC	Pathogenic	0.95
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	1.0	D
M_CAP	Uncertain	0.17	D
MetaRNN	Uncertain	0.54	D
MetaSVM	Pathogenic	0.87	D
MutationAssessor	Pathogenic	4.5	H
PhyloP100		7.8
PrimateAI	Uncertain	0.67	T
PROVEAN	Pathogenic	-5.1	D
REVEL	Pathogenic	0.89
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.96
MVP		0.95
MPC		0.46
ClinPred		0.55	D
GERP RS		5.3
Varity_R		0.80
gMVP		0.90
Mutation Taster		=20/80	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: rs190814907; hg19: chr2-128327387; COSMIC: COSV105330775;