rs41315966

Variant names:

• chr15-66490389-C-T
• rs41315966
• NM_002755.4:c.1069-113C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_006049.4(SNAPC5):​c.*350G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00164 in 838,584 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0012 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0017 (3 hom.)
• Consequence: SNAPC5 NM_006049.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.289
• Publications: 1 publications found

Genes affected

MAP2K1 (HGNC:6840): (mitogen-activated protein kinase kinase 1) The protein encoded by this gene is a member of the dual specificity protein kinase family, which acts as a mitogen-activated protein (MAP) kinase kinase. MAP kinases, also known as extracellular signal-regulated kinases (ERKs), act as an integration point for multiple biochemical signals. This protein kinase lies upstream of MAP kinases and stimulates the enzymatic activity of MAP kinases upon wide variety of extra- and intracellular signals. As an essential component of MAP kinase signal transduction pathway, this kinase is involved in many cellular processes such as proliferation, differentiation, transcription regulation and development. [provided by RefSeq, Jul 2008]

ENSG00000261351 (HGNC:):

SNAPC5 (HGNC:15484): (small nuclear RNA activating complex polypeptide 5) This gene encodes a subunit of the small nuclear RNA (snRNA)-activating protein complex that plays a role in the transcription of snRNA genes. This complex binds to the promoters of snRNA genes transcribed by either RNA polymerase II or III and recruits other regulatory factors to activate snRNA gene transcription. The encoded protein may play a role in stabilizing this complex. A pseudogene of this gene has been identified on chromosome 6. [provided by RefSeq, Jul 2016]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 15-66490389-C-T is Benign according to our data. Variant chr15-66490389-C-T is described in ClinVar as Benign. ClinVar VariationId is 1239027.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006049.4. 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
	MAP2K1	NM_002755.4	MANE Select	c.1069-113C>T		intron	N/A	NP_002746.1	Q02750-1
	SNAPC5	NM_006049.4		c.*350G>A		3_prime_UTR	Exon 4 of 4	NP_006040.1	O75971-1
	MAP2K1	NM_001411065.1		c.925-113C>T		intron	N/A	NP_001397994.1	A0A8I5KYS7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP2K1	ENST00000307102.10	TSL:1 MANE Select	c.1069-113C>T		intron	N/A	ENSP00000302486.5	Q02750-1
	ENSG00000261351	ENST00000565387.2	TSL:1	n.437G>A		non_coding_transcript_exon	Exon 2 of 2
	SNAPC5	ENST00000395589.6	TSL:2	c.*350G>A		3_prime_UTR	Exon 4 of 4	ENSP00000378954.2	O75971-1

Frequencies

GnomAD3 genomes AF: 0.00125 AC: 190 AN: 152216 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000314

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00367

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00195

Gnomad OTH AF: 0.000955

GnomAD2 exomes AF: 0.00143 AC: 338 AN: 235936 AF XY: 0.00144

Gnomad AFR exome AF: 0.000202

Gnomad AMR exome AF: 0.0000882

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00697

Gnomad NFE exome AF: 0.00203

Gnomad OTH exome AF: 0.00170

GnomAD4 exome AF: 0.00173 AC: 1185 AN: 686250 Hom.: 3 Cov.: 9 AF XY: 0.00173 AC XY: 641 AN XY: 370196

African (AFR) AF: 0.000423 AC: 8 AN: 18926

American (AMR) AF: 0.0000924 AC: 4 AN: 43282

Ashkenazi Jewish (ASJ) AF: 0.000141 AC: 3 AN: 21316

East Asian (EAS) AF: 0.00 AC: 0 AN: 36174

South Asian (SAS) AF: 0.00 AC: 0 AN: 70318

European-Finnish (FIN) AF: 0.00740 AC: 312 AN: 42136

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4256

European-Non Finnish (NFE) AF: 0.00198 AC: 820 AN: 414782

Other (OTH) AF: 0.00108 AC: 38 AN: 35060

GnomAD4 genome AF: 0.00125 AC: 190 AN: 152334 Hom.: 0 Cov.: 33 AF XY: 0.00124 AC XY: 92 AN XY: 74490

African (AFR) AF: 0.000313 AC: 13 AN: 41588

American (AMR) AF: 0.000131 AC: 2 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

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

European-Finnish (FIN) AF: 0.00367 AC: 39 AN: 10618

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

European-Non Finnish (NFE) AF: 0.00196 AC: 133 AN: 68028

Other (OTH) AF: 0.000945 AC: 2 AN: 2116

Alfa AF: 0.00121 Hom.: 0

Bravo AF: 0.000831

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.2
DANN	Benign	0.74
PhyloP100		-0.29
Mutation Taster		=100/0	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: rs41315966; hg19: chr15-66782727;