3-47622292-AAGA-G

Position:

• chr3-47622292-AAGA-G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PM4_Supporting PP3 PP5_Moderate

The NM_003074.4(SMARCC1):​c.2693_2696delTCTTinsC​(p.Leu898_Leu899delinsPro) variant causes a missense, disruptive inframe deletion change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SMARCC1 NM_003074.4 missense, disruptive_inframe_deletion
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 9.32

Genes affected

SMARCC1 (HGNC:11104): (SWI/SNF related, matrix associated, actin dependent regulator of chromatin subfamily c 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 contains a predicted leucine zipper motif typical of many transcription factors. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_003074.4. Strenght limited to Supporting due to length of the change: 1aa.
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
• PP5: Variant 3-47622292-AAGA-G is Pathogenic according to our data. Variant chr3-47622292-AAGA-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1321260.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMARCC1	NM_003074.4	c.2693_2696delTCTTinsC	p.Leu898_Leu899delinsPro	missense_variant, disruptive_inframe_deletion	25/28	ENST00000254480.10	NP_003065.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMARCC1	ENST00000254480.10	c.2693_2696delTCTTinsC	p.Leu898_Leu899delinsPro	missense_variant, disruptive_inframe_deletion	25/28	1	NM_003074.4	ENSP00000254480.5
SMARCC1	ENST00000425518.5	n.2583_2586delTCTTinsC		non_coding_transcript_exon_variant	25/28	2

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Global developmental delay Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

3billion

Oct 25, 2021

Inframe deletion located in a nonrepeat region: predicted to change the length of the protein and disrupt normal protein function (PM4). The variant was observed as assumed (i.e. paternity and maternity not confirmed) de novo (3billion dataset, PM6). It is not observed in the gnomAD v2.1.1 dataset (PM2). Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline. -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-47663782;