rs1164377600

Variant names:

• chr1-203169351-A-G
• rs1164377600
• NM_004997.3:c.1132T>C

Your query was ambiguous. Multiple possible variants found:

• chr1-203169351-A-G
• chr1-203169351-A-C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_004997.3(MYBPH):​c.1132T>C​(p.Phe378Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000138 in 1,450,202 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: MYBPH NM_004997.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.72
• Publications: 0 publications found

Genes affected

MYBPH (HGNC:7552): (myosin binding protein H) Predicted to be a structural constituent of muscle. Predicted to be involved in regulation of striated muscle contraction. Predicted to be located in myosin filament. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30417836).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004997.3. 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
	MYBPH	NM_004997.3	MANE Select	c.1132T>C	p.Phe378Leu	missense	Exon 8 of 11	NP_004988.2	Q13203

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYBPH	ENST00000255416.9	TSL:1 MANE Select	c.1132T>C	p.Phe378Leu	missense	Exon 8 of 11	ENSP00000255416.4	Q13203
	MYBPH	ENST00000966288.1		c.1207T>C	p.Phe403Leu	missense	Exon 8 of 10	ENSP00000636347.1
	MYBPH	ENST00000966289.1		c.1207T>C	p.Phe403Leu	missense	Exon 8 of 11	ENSP00000636348.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000443 AC: 1 AN: 225758 AF XY: 0.00000819

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000312

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1450202 Hom.: 0 Cov.: 33 AF XY: 0.00000278 AC XY: 2 AN XY: 720358

African (AFR) AF: 0.00 AC: 0 AN: 33330

American (AMR) AF: 0.0000234 AC: 1 AN: 42824

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25738

East Asian (EAS) AF: 0.00 AC: 0 AN: 39402

South Asian (SAS) AF: 0.00 AC: 0 AN: 84972

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52684

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1105564

Other (OTH) AF: 0.0000167 AC: 1 AN: 59928

GnomAD4 genome Cov.: 33

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	Pathogenic	0.84
BayesDel_addAF	Benign	-0.095	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.096	T
Eigen	Benign	0.16
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		4.7
PrimateAI	Uncertain	0.56	T
PROVEAN	Pathogenic	-4.9	D
REVEL	Benign	0.13
Sift	Benign	0.053	T
Sift4G	Uncertain	0.019	D
Polyphen		0.33	B
Vest4		0.33
MutPred		0.48		Gain of disorder (P = 0.2134)
MVP		0.71
MPC		0.20
ClinPred		0.98	D
GERP RS		5.3
Varity_R		0.58
gMVP		0.62
Mutation Taster		=89/11	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: rs1164377600; hg19: chr1-203138479;