Genetic Variant NM_005527.4:c.1477_1479delACGinsCGC (chr6-31810494-CGT-GCG) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is The variant received 2 classification points (ACMG Germline Pathogenicity v2019). PM2

The NM_005527.4(HSPA1L):c.1477_1479delACGinsCGC (p.Thr493Arg) variant causes a missense change. Note: allele frequency estimates from gnomAD may be inaccurate for this variant type (MNP or indel longer than 3 bp) due to technology limitations. The variant is absent from the gnomAD population database at sites with sufficient sequencing coverage. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Other variants at the same amino acid position have been reported in ClinVar (not pathogenic): p.T493K: association (ClinVar VariationId 694520, 0 stars); p.T493M: Benign (ClinVar VariationId 3060421, 0 stars)

Frequency

Genomes: not found (cov: 31)

Consequence

HSPA1L
NM_005527.4 missense

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.09

Publications

0 publications found

Variant links:

Genes affected

HSPA1L (HGNC:5234): (heat shock protein family A (Hsp70) member 1 like) This gene encodes a 70kDa heat shock protein. In conjunction with other heat shock proteins, this protein stabilizes existing proteins against aggregation and mediates the folding of newly translated proteins in the cytosol and in organelles. The gene is located in the major histocompatibility complex class III region, in a cluster with two closely related genes which also encode isoforms of the 70kDa heat shock protein. [provided by RefSeq, Jul 2008]

HSPA1L Gene-Disease associations (from GenCC):

inflammatory bowel disease
Inheritance: AD Classification: MODERATE Submitted by: PanelApp Australia

HSPA1L links:

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new If you want to explore the variant's impact on the transcript NM_005527.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript:

Our verdict: Uncertain_significance. The variant received 2 points.

Show applied only (1)

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	PM2Absent/extremely low in population databases		Absent from gnomAD (AD/XL gene) — PM2; Absent from gnomAD at well-covered site (MOI: AD/XL) (threshold 0.0001) — PM2 moderate.

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_005527.4. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	HSPA1L NM_005527.4	MANE Select	c.1477_1479delACGinsCGC p.Thr493Arg	missense	N/A	Prot: NP_005518.3

HSPA1L NM_005527.4

MANE Select

HGVSc / HGVSpc.1477_1479delACGinsCGCp.Thr493Arg

Exon rankN/A

missense

Prot: NP_005518.3

Ensembl Transcripts

Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
HSPA1L ENST00000375654.5	TSL:1MANE Select	c.1477_1479delACGinsCGC p.Thr493Arg	missense	N/A	Prot: ENSP00000364805.4 UniProt: P34931
HSPA1L ENST00000879288.1		c.1477_1479delACGinsCGC p.Thr493Arg	missense	N/A	Prot: ENSP00000549347.1 UniProt: P34931
HSPA1L ENST00000879289.1		c.1477_1479delACGinsCGC p.Thr493Arg	missense	N/A	Prot: ENSP00000549348.1 UniProt: P34931

HSPA1L ENST00000375654.5

TSL:1MANE Select

HGVSc / HGVSpc.1477_1479delACGinsCGCp.Thr493Arg

Exon rankN/A

missense

Prot: ENSP00000364805.4UniProt: P34931

HSPA1L ENST00000879288.1

HGVSc / HGVSpc.1477_1479delACGinsCGCp.Thr493Arg

Exon rankN/A

missense

Prot: ENSP00000549347.1UniProt: P34931

HSPA1L ENST00000879289.1

HGVSc / HGVSpc.1477_1479delACGinsCGCp.Thr493Arg

Exon rankN/A

missense

Prot: ENSP00000549348.1UniProt: P34931

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 2 sources Large-scale international reference populations
GnomAD3 genomes	AF:	AC:	Hom:	AN:	Cov:31
GnomAD4 genome	AF:	AC:	Hom:	AN:	Cov:31

Showing 2 sources

Tested, but no data found:GnomAD4 exomeIf GnomAD4 is missing, the position is probably not covered by the project.

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
PhyloP100	Uncertain	4.1

Showing 1 of 1 scores

Splicing Scores

No splicing scores have been computed for this variant.

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACMG Germline Pathogenicity v2019

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational Scores

Splicing Scores

MaveDB functional evidence ?

Publications

Other links and lift over

MaveDB functional evidence