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GeneBe

14-54568111-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_015589.6(SAMD4A):c.195C>T(p.Pro65=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000998 in 1,513,208 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0052 ( 11 hom., cov: 32)
Exomes 𝑓: 0.00052 ( 5 hom. )

Consequence

SAMD4A
NM_015589.6 splice_region, synonymous

Scores

2
Splicing: ADA: 0.00007261
2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.35
Variant links:
Genes affected
SAMD4A (HGNC:23023): (sterile alpha motif domain containing 4A) Sterile alpha motifs (SAMs) in proteins such as SAMD4A are part of an RNA-binding domain that functions as a posttranscriptional regulator by binding to an RNA sequence motif known as the Smaug recognition element, which was named after the Drosophila Smaug protein (Baez and Boccaccio, 2005 [PubMed 16221671]).[supplied by OMIM, Mar 2008]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.57).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 14-54568111-C-T is Benign according to our data. Variant chr14-54568111-C-T is described in ClinVar as [Benign]. Clinvar id is 711102.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-54568111-C-T is described in Lovd as [Likely_benign].
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-1.35 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00524 (798/152198) while in subpopulation AFR AF= 0.0181 (753/41514). AF 95% confidence interval is 0.0171. There are 11 homozygotes in gnomad4. There are 387 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 793 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SAMD4ANM_015589.6 linkuse as main transcriptc.195C>T p.Pro65= splice_region_variant, synonymous_variant 2/13 ENST00000554335.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SAMD4AENST00000554335.6 linkuse as main transcriptc.195C>T p.Pro65= splice_region_variant, synonymous_variant 2/135 NM_015589.6 A1Q9UPU9-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00521
AC:
793
AN:
152094
Hom.:
11
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0181
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00190
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:
0.0000882
Gnomad OTH
AF:
0.00431
GnomAD3 exomes
AF:
0.00109
AC:
137
AN:
125946
Hom.:
2
AF XY:
0.000883
AC XY:
62
AN XY:
70220
show subpopulations
Gnomad AFR exome
AF:
0.0254
Gnomad AMR exome
AF:
0.000761
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000878
Gnomad OTH exome
AF:
0.000852
GnomAD4 exome
AF:
0.000523
AC:
712
AN:
1361010
Hom.:
5
Cov.:
32
AF XY:
0.000450
AC XY:
302
AN XY:
670738
show subpopulations
Gnomad4 AFR exome
AF:
0.0188
Gnomad4 AMR exome
AF:
0.00114
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000647
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000551
Gnomad4 OTH exome
AF:
0.00127
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00524
AC:
798
AN:
152198
Hom.:
11
Cov.:
32
AF XY:
0.00520
AC XY:
387
AN XY:
74394
show subpopulations
Gnomad4 AFR
AF:
0.0181
Gnomad4 AMR
AF:
0.00196
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000882
Gnomad4 OTH
AF:
0.00427
Alfa
AF:
0.000135
Hom.:
0
Bravo
AF:
0.00603

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeFeb 13, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.57
Cadd
Benign
1.9
Dann
Benign
0.95

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.000073
dbscSNV1_RF
Benign
0.11
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs200235203; hg19: chr14-55034829; API