Genetic Variant SMARCD1:p.Leu48Pro (chr12-50085512-T-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_003076.5(SMARCD1):c.143T>C(p.Leu48Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L48V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SMARCD1
NM_003076.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.73

Publications

0 publications found

Variant links:

Genes affected

SMARCD1 (HGNC:11106): (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily d, member 1) The protein encoded by this gene is a member of the SWI/SNF family of proteins, whose members display helicase and ATPase activities and which are thought to regulate transcription of certain genes by altering the chromatin structure around those genes. The encoded protein is part of the large ATP-dependent chromatin remodeling complex SNF/SWI and has sequence similarity to the yeast Swp73 protein. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

SMARCD1 Gene-Disease associations (from GenCC):

Coffin-Siris syndrome 11
Inheritance: AD Classification: STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
neurodevelopmental disorder
Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia
Coffin-Siris syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

SMARCD1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003076.5. 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
	SMARCD1	NM_003076.5	MANE Select	c.143T>C	p.Leu48Pro	missense	Exon 1 of 13	NP_003067.3
	SMARCD1	NM_139071.3		c.143T>C	p.Leu48Pro	missense	Exon 1 of 12	NP_620710.2	Q96GM5-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SMARCD1	ENST00000394963.9	TSL:1 MANE Select	c.143T>C	p.Leu48Pro	missense	Exon 1 of 13	ENSP00000378414.4	Q96GM5-1
SMARCD1	ENST00000381513.8	TSL:1	c.143T>C	p.Leu48Pro	missense	Exon 1 of 12	ENSP00000370924.4	Q96GM5-2
SMARCD1	ENST00000547247.5	TSL:1	n.171T>C		non_coding_transcript_exon	Exon 1 of 6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1086074

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

513670

African (AFR)

AF:

0.00

AC:

AN:

23140

American (AMR)

AF:

0.00

AC:

AN:

9124

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14416

East Asian (EAS)

AF:

0.00

AC:

AN:

26752

South Asian (SAS)

AF:

0.00

AC:

AN:

19870

European-Finnish (FIN)

AF:

0.00

AC:

AN:

23308

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2942

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

922732

Other (OTH)

AF:

0.00

AC:

AN:

43790

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Pathogenic

0.25

BayesDel_noAF

Uncertain

0.12

CADD

Uncertain

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.053

Eigen

Benign

0.13

Eigen_PC

Benign

0.19

FATHMM_MKL

Benign

0.44

LIST_S2

Benign

0.76

M_CAP

Pathogenic

1.0

MetaRNN

Uncertain

0.47

MetaSVM

Uncertain

0.12

MutationAssessor

Benign

0.69

PhyloP100

3.7

PrimateAI

Pathogenic

0.95

PROVEAN

Benign

0.76

REVEL

Uncertain

0.51

Sift

Benign

0.36

Sift4G

Benign

0.34

Polyphen

0.0

Vest4

0.61

MutPred

0.24

Loss of sheet (P = 0.0142)

MVP

0.78

MPC

2.2

ClinPred

0.70

GERP RS

4.7

PromoterAI

0.10

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.40

gMVP

0.49

Mutation Taster

=43/57

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over