19-38587707-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001042600.3(MAP4K1):c.*41C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00166 in 1,439,774 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0015 (2 hom., cov: 31)
  • Exomes 𝑓: 0.0017 (22 hom.)
• Consequence: MAP4K1 NM_001042600.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.185

Genes affected

MAP4K1 (HGNC:6863): (mitogen-activated protein kinase kinase kinase kinase 1) Enables ATP binding activity and MAP kinase kinase kinase kinase activity. Involved in several processes, including JNK cascade; cellular response to phorbol 13-acetate 12-myristate; and protein phosphorylation. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

RYR1 (HGNC:10483): (ryanodine receptor 1) This gene encodes a ryanodine receptor found in skeletal muscle. The encoded protein functions as a calcium release channel in the sarcoplasmic reticulum but also serves to connect the sarcoplasmic reticulum and transverse tubule. Mutations in this gene are associated with malignant hyperthermia susceptibility, central core disease, and minicore myopathy with external ophthalmoplegia. Alternatively spliced transcripts encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 19-38587707-G-C is Benign according to our data. Variant chr19-38587707-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 1223674.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAP4K1	NM_001042600.3	c.*41C>G		3_prime_UTR_variant	31/31	ENST00000396857.7
MAP4K1	NM_007181.6	c.*103C>G		3_prime_UTR_variant	32/32
MAP4K1	XM_011526404.2	c.*41C>G		3_prime_UTR_variant	32/32

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAP4K1	ENST00000396857.7	c.*41C>G		3_prime_UTR_variant	31/31	5	NM_001042600.3	P1

Frequencies

GnomAD3 genomes AF: 0.00140 AC: 213 AN: 152188 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.00183

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00105

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0101

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000867

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00247 AC: 613 AN: 248062 Hom.: 4 AF XY: 0.00311 AC XY: 418 AN XY: 134558

Gnomad AFR exome AF: 0.00227

Gnomad AMR exome AF: 0.00169

Gnomad ASJ exome AF: 0.00180

Gnomad EAS exome AF: 0.0000555

Gnomad SAS exome AF: 0.0120

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00109

Gnomad OTH exome AF: 0.00216

GnomAD4 exome AF: 0.00168 AC: 2167 AN: 1287468 Hom.: 22 Cov.: 19 AF XY: 0.00212 AC XY: 1375 AN XY: 649826

Gnomad4 AFR exome AF: 0.00378

Gnomad4 AMR exome AF: 0.00176

Gnomad4 ASJ exome AF: 0.00192

Gnomad4 EAS exome AF: 0.0000257

Gnomad4 SAS exome AF: 0.0121

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000779

Gnomad4 OTH exome AF: 0.00220

GnomAD4 genome AF: 0.00145 AC: 221 AN: 152306 Hom.: 2 Cov.: 31 AF XY: 0.00158 AC XY: 118 AN XY: 74458

Gnomad4 AFR AF: 0.00200

Gnomad4 AMR AF: 0.00105

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0104

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000867

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00150 Hom.: 0

Bravo AF: 0.00145

Asia WGS AF: 0.00808 AC: 28 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 07, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	3.0
Dann	Benign	0.66

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

Publications

LitVar

Other links and lift over

dbSNP: rs113000039; hg19: chr19-39078347;