rs368405203

Variant names:

• chr8-2949343-T-C
• rs368405203
• NM_033225.6:c.10358A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_033225.6(CSMD1):​c.10358A>G​(p.Asp3453Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,608,384 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: CSMD1 NM_033225.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.08
• Publications: 0 publications found

Genes affected

CSMD1 (HGNC:14026): (CUB and Sushi multiple domains 1) Predicted to act upstream of or within several processes, including learning or memory; mammary gland branching involved in pregnancy; and reproductive structure development. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

CSMD1 Gene-Disease associations (from GenCC):

• autism spectrum disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• complex neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

LOC105377785 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.072484255).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033225.6. 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
	CSMD1	NM_033225.6	MANE Select	c.10358A>G	p.Asp3453Gly	missense	Exon 68 of 70	NP_150094.5
	LOC105377785	NR_168441.1		n.1167-51662T>C		intron	N/A
	LOC105377785	NR_168442.1		n.2191+22713T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSMD1	ENST00000635120.2	TSL:5 MANE Select	c.10358A>G	p.Asp3453Gly	missense	Exon 68 of 70	ENSP00000489225.1	Q96PZ7-1
	CSMD1	ENST00000335551.11	TSL:1	c.8564A>G	p.Asp2855Gly	missense	Exon 54 of 56	ENSP00000334828.6	H7BXU2
	CSMD1	ENST00000520002.5	TSL:5	c.10361A>G	p.Asp3454Gly	missense	Exon 69 of 71	ENSP00000430733.1	E5RIG2

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 151994 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000836 AC: 2 AN: 239360 AF XY: 0.00000767

Gnomad AFR exome AF: 0.0000659

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000912

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000103 AC: 15 AN: 1456390 Hom.: 0 Cov.: 28 AF XY: 0.00000690 AC XY: 5 AN XY: 724736

African (AFR) AF: 0.00 AC: 0 AN: 33350

American (AMR) AF: 0.00 AC: 0 AN: 44540

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26028

East Asian (EAS) AF: 0.00 AC: 0 AN: 39440

South Asian (SAS) AF: 0.00 AC: 0 AN: 85898

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52242

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5740

European-Non Finnish (NFE) AF: 0.0000135 AC: 15 AN: 1108972

Other (OTH) AF: 0.00 AC: 0 AN: 60180

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 151994 Hom.: 0 Cov.: 33 AF XY: 0.0000404 AC XY: 3 AN XY: 74234

African (AFR) AF: 0.0000241 AC: 1 AN: 41424

American (AMR) AF: 0.00 AC: 0 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10556

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 67996

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.0000508 Hom.: 0

Bravo AF: 0.0000113

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000123 AC: 1

ExAC AF: 0.0000166 AC: 2

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	Benign	0.25
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	18
DANN	Benign	0.94
DEOGEN2	Benign	0.021	T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.072	T
MetaSVM	Benign	-1.0	T
PhyloP100		2.1
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.066
Sift	Benign	0.63	T
Sift4G	Benign	0.41	T
Polyphen		0.049	B
Vest4		0.49
MVP		0.20
ClinPred		0.075	T
GERP RS		4.4
Varity_R		0.22
gMVP		0.45
Mutation Taster		=92/8	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: rs368405203; hg19: chr8-2806865;